Herbicidal glutarimides

ABSTRACT

This invention relates to glutarimide compounds exhibiting herbicidal activity having the structure ##STR1## wherein A is carbonyl, thiocarbonyl or methylene, Al is carbonyl or methylene, Q is O or (CH 2 ) n  where n is 0 or 1, D is CH or N and R, R 1 , R 2 , T, X, Y and Z are as defined within, compositions containing these compounds and methods of using these compounds as herbicides and algicides.

This is a divisional of application Ser. No. 129,483, filed Sep. 30,1993, now U.S. Pat. No. 5,393,735, which is a continuation of U.S. Ser.No. 563,780 filed Aug. 9, 1990 abandoned; which is acontinuation-in-part of U.S. Ser. No. 401,329 filed Aug. 31, 1989abandoned.

This invention relates to novel glutarimides which have activity asherbicides and algicides, to compositions which contain these compoundsand to methods of use of these compounds.

BACKGROUND OF THE INVENTION

During the past years, there has been an intensified search forherbicides to control unwanted plants. U.S. Pat. No. 4,400,202 disclosesN-(m-phenylglutarimido)ureas and N-(m-phenylsuccinimido)ureas and theiruse as herbicides. No other substitution on the phenyl ring isdisclosed.

U.S. Pat. No. 4,595,408 discloses N-(m-amidophenyl)succinimides andN-(m-amidophenyl)glutarimides and their use as herbicides. No othersubstitution on the phenyl ring is disclosed.

There remains a need for additional herbicidal agents which are aseffective or more effective than presently existing compounds.

SUMMARY OF THE INVENTION

The present invention is a new class of substituted cyclic imides theformula ##STR2## wherein

A is carbonyl (C═O), thiocarbonyl (C═S) or methylene (CH₂);

A¹ is carbonyl (C═O) or methylene (CH₂);

provided that when Z is hydrogen (H), A and A¹ are not both CH₂ ;

D is CH or, when X is hydrogen, nitrogen (N);

Q is methylene ((CH₂)_(n)), where n is 0 or 1, or oxygen (O);

R is (C₁ -C₄)alkyl, (C₁ -C₄)haloalkyl containing from one to nine haloatoms, or phenyl;

R¹ is hydrogen or (C₁ -C₂)alkyl; provided R¹ is hydrogen when X and Zare independently hydrogen or halogen and Y is halogen;

R² is hydrogen; or

R, R¹ and R² taken together form a fused phenyl ring;

X is hydrogen, cyano (CN) or halogen;

Y is hydrogen, halogen, cyano (CN), (C₁ -C₃)alkylthio, halo(C₁-C₃)alkylthio, (C₁ -C₃)alkyl, halo(C₁ -C₃)alkyl, nitro, halo(C₁-C₃)alkoxy or (C₁ -C₃)alkoxy;

provided when Y is hydrogen, R is trifluoromethyl (CF₃), R¹ and R² arehydrogen and Z is not hydrogen;

T is hydrogen or fluorine; and

Z is hydrogen; hydroxy (OH); halogen; cyano; thiol (SH);alkylsulfonyloxy (--OSO₂ alkyl); phenylsulfonyloxy (--OSO₂ phenyl);alkyl; alkoxy; alkenyloxy; alkynyloxy; cydoalkoxy; cycloalkylalkoxy;phenylalkoxy; alkylthio; alkenylthio; alkynylthio; cycloalkylthio;cycloalkylalkylthio; phenylalkylthio; alkanoyloxy; alkanoylthio;alkoxycarbonylalkylthio; alkoxycarbonylalkoxy;alkoxycarbonyl(alkoxy)alkoxy; alkoxyalkoxy; (alkylthio)alkoxy;alkoxyalkylthio; alkylthioalkylthio; (phenylthio)alkoxy; phenoxyalkoxy;phenylthioalkylthio; phenoxyalkylthio; carboxyalkylthio;carboxyalkoxy;(heterocycyloxy;heterocyclylalkyloxy; carboxy; formyl;alkylcarbonyl; alkoxycarbonyl; (alkylthio)carbonyl;alkoxycarbonylalkoxycarbonyl; phenoxycarbonyl; alkoxyalkoxycarbonyl;alkenyloxycarbonyl; alkynyloxycarbonyl; cydoalkoxycarbonyl;cycloalkylalkoxycarbonyl; (alkenylthio)carbonyl; (alkynylthio)carbonyl;(cycloalkylthio)carbonyl; (cycloalkylalkylthio)carbonyl;heterocydylcarbonyl; heterocydylalkoxycarbonyl; heterocydyloxycarbonyl;trialkylsilylalkoxycarbonyl; dialkoxyphosphonylalkoxycarbonyl(--C(═O)OalkylP(═O)(alkoxy)₂); dialkyliminooxycarbonyl(--C(═O)ON═C(alkyl)₂); alkyliminooxycarbonyl;alkyl(alkoxy)iminooxycarbonyl; alkyl(alkylthio)iminooxycarbonyl;phenylaminocarbonyl; aminocarbonyl; alkylaminocarbonyl;alkenylaminocarbonyl; alkynylaminocarbonyl; alkoxyaminocarbonyl;alkoxyalkyl; alkenyloxyalkyl; alkynyloxyalkyl; cydoalkoxyalkyl;cydoalkylalkoxyalkyl; alkanoyloxyalkyl; alkylthioalkyl;alkenylthioalkyl; alkynylthioalkyl; cycloalkylthioalkyl;cycloalkylalkylthioalkyl; (alkanoylthio)alkyl; phenoxyalkyl;phenylthioalkyl; alkoxycarbonylalkoxyalkyl; oximyl (--CH═NOH);alkyloximyl (--CH═NOalkyl); alkenyloximyl (--CH═NOalkenyl);alkynyloximyl (--CH═NOalkynyl); alkoxycarbonylalkyloximyl(--CH═NO(alkoxycarbonyl)alkyl); alkyl(alkoxy)oximyl(--C(alkoxy)═NOalkyl); alkenyl(alkoxy)oximyl (--C(alkoxy)═NOalkenyl);alkynyl(alkoxy)oximyl (--C(alkoxy)═NOalkynyl);alkoxycarbonylalkyl(alkoxy)oximyl (--C(alkoxy)═NO(alkoxycarbonyl)alkyl);alkyl(alkyl)oximyl (--C(alkyl)═NOalkyl); alkenyl(alkyl)oximyl(--C(alkyl)═NOalkenyl); alkynyl(alkyl)oximyl (--C(alkyl)═NOalkynyl);alkoxycarbonylalkyl-(alkyl)oximyl (--C(alkyl)═NO(alkoxycarbonyl)alkyl);alkyl(alkylthio)oximyl (--C(alkylthio)═NOalkyl);alkenyl(alkylthio)oximyl (--C(alkylthio)═NOalkenyl);alkynyl(alkylthio)oximyl (--C(alkylthio)═NOalkynyl);alkoxycarbonylalkyl(alkylthio)oximyl(--C(alkylthio)═NO(alkoxycarbonyl)alkyl);heterocyclyl; alkylamino; alkenylamino; alkynylamino; or alkanoylamino;

provided Z is not hydrogen when X and Y are both bromine (Br) orchlorine (Cl) and D is CH; or

Z and Y together form a 5- or 6-membered heterocyclic ring fused to thephenyl ring structure to form a bicyclic moiety having the structure##STR3## wherein

L is oxygen (O) or sulfur (S);

R³ is hydrogen or alkyl;

R⁴ is hydrogen; alkyl; alkenyl; alkynyl; alkoxyalkyl; alkenyloxyalkyl;alkynyloxyalkyl; cyanoalkyl; alkoxycarbonylalkyl; cycloalkyl;cycloalkylalkyl; phenylalkyl; alkylthioalkyl; alkenylthioalkyl;alkynylthioalkyl; heterocydyl; heterocyclylalkyl; alkylaminoalkyl;alkylaminocarbonylalkyl; alkoxycarbonyl; or alkanoyl; and

R⁵ is hydrogen, (C₁ -C₃)alkyl or fluorine. Also included are theagronomically acceptable salts thereof.

Alkyl means straight and branched alkyl groups, for example (C₁-C₈)alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,s-butyl, 1-ethylpropyl or n-octyl. An alkyl portion of any one of thesubstituents listed above for Z is optionally substituted by one to fivehalogens to form groups such as trifluoromethyl,1,1,1,2,2-pentafluoroethyl or (trifluoromethyl)methyl; optionallysubstituted by phenyl to form groups such as benzyl or phenethyl; oroptionally substituted by cyano to form groups such as cyanomethyl,2-cyanoethyl or 1-cyanoethyl. Cycloalkyl is, for example, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl and includes cycloalkyl optionallysubstituted by (C₁ -C₄)alkyl, for example 2-methylcyclopropyl, or halo,for example 2,2-dichlorocydopropyl. Phenyl is optionally substitutedwith one or two substituents such as (C₁ -C₃)alkyl, halogen, (C₁-C₃)alkoxy or trifluoromethyl. Haloalkyl for R is, for example,fluoromethyl, difluoromethyl, trifluoromethyl, or pentafluoroethyl.

Heterocydyl means a three to six membered heterocyclic ring containingone, two or three heteroatoms such as oxygen, nitrogen or sulfur andincludes saturated and unsaturated figs, for example tetrahydrofuryl,furyl, epoxy, pyridyl, piperidyl, dioxolanyl, isoxazolidinyl, triazolyl,thienyl, thiazolyl or piperazyl, optionally substituted by one to three(C₁ -C₆)alkyl groups for example, 5,5-dimethyloxazolinyl.

Halogen means fluorine, chlorine, bromine and iodine.

When listed for Y and Z, thio means thio (--S--). When not bonded tocarbonyl, thio also includes sulfinyl (--SO--) and sulfonyl (--SO₂ --).

Substituted amino groups such as alkylamino include mono- anddi-substituted groups for example monoalkylamino and dialkylamino.

Oximes are in either the syn or anti configuration or are mixturesthereof.

Agronomically acceptable salts include those known in the art, forexample, metal salts such as sodium, potassium, calcium and magnesium,ammonium salts such as isopropylammonium and trialkylsulfonium saltssuch as trimethylsulfonium.

Alkoxy is, for example, (C₁ -C₆)alkoxy such as methoxy, ethoxy,n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, or s-butyloxy.Alkenyloxy is, for example, (C₃ -C₆)alkenyloxy such as allyloxy,2-chloroallyloxy or 3,3-dichloroallyloxy. Alkynyloxy is, for example,(C₃ -C₆)alkynyloxy such as propargyloxy, 1-methylpropargyloxy,1-(3-butynyl)oxy or 1-(2-butynyl)oxy. Phenylalkoxy is, for example,phenyl(C₁ -C₆)alkoxy such as phenylmethoxy. Alkylthio is, for example,(C₁ -C₆)alkylthio such as methylthio, ethylthio, propylthio, butylthio.Alkenylthio is, for example, (C₃ -C₆)alkenylthio. Alkynylthio is, forexample, (C₃ -C₆)alkynylthio. Phenylalkylthio is, for example, phenyl(C₁-C₆)alkylthio. Alkanoyloxy is, for example, (C₁ -C₆)alkanoyloxy.Alkanoylthio is, for example, (C₁ -C₆)alkanoylthio such as acetylthio.Alkoxycarbonylalkylthio is, for example, (C₁ -C₆)alkoxycarbonyl(C₁-C₄)alkylthio such as methoxycarbonylmethylthio orisopropyloxycarbonylmethylthio. Alkoxycarbonylalkoxy is, for example,(C₁ -C₆)alkoxycarbonyl(C₁ -C₄)alkoxy such as methoxycarbonylmethoxy.Alkoxycarbonyl(alkoxy)alkoxy is, for example, (C₁ -C₆)alkoxycarbonyl((C₁-C₆)alkoxy)(C₁ -C₆)alkoxy such as methoxycarbonyl(methoxy)methoxy.Alkoxyalkoxy is, for example, (C₁ -C₆)alkoxy(C₁ -C₆)alkoxy such asmethoxymethoxy or 2-methoxyethoxy. (Alkylthio)alkoxy is, for example,((C₁ -C₆)alkylthio)(C₁ -C₆)alkoxy. Alkoxyalkylthio is, for example, (C₁-C₆)alkoxy(C₁ - C₆)alkylthio. Alkylthoalkylthio is, for example, (C₁-C₆)alkylthio(C₁ -C₆)alkylthio. (Phenylthio)alkoxy is, for example,(phenylthio)(C₁ -C₆)alkoxy such as (phenylthio)methoxy. Phenoxyalkoxyis, for example, phenoxy(C₁ -C₆)alkoxy. Phenylthioalkylthio is, forexample, phenylthio(C₁ -C₆)alkylthio. Phenoxyalkylthio is, for example,phenoxy(C₁ -C₆)alkylthio. Carboxyalkylthio is, for example, carboxy(C₁-C₆)alkylthio. Carboxyalkoxy is, for example, carboxy(C₁ -C₆)alkoxy suchas carboxymethoxy. Alkylcarbonyl is, for example (C₁ -C₆)alkylcarbonylsuch as methylcarbonyl, i.e. acetyl. Alkoxycarbonyl is, for example,(C₁ - C₆)alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl,n-propyloxycarbonyl, isopropyloxycarbonyl, 1-cyanoethoxycarbonyl,isobutyloxycarbonyl or s-butyloxycarbonyl. (Alkylthio)carbonyl is, forexample, ((C₁ -C₆)alkylthio)carbonyl such as (ethylthio)carbonyl or(isopropylthio)carbonyl. Alkoxycarbonylalkoxycarbonyl is, for example,(C₁ -C₆)alkoxycarbonyl(C₁ -C₆)alkoxycarbonyl such asmethoxycarbonyl(methyl)methoxycarbonyl orethoxycarbonyl-methoxycarbonyl. Alkoxyalkoxycarbonyl is, for example,(C₁ -C₆)alkoxy(C₁ C₆)alkoxycarbonyl such as (2-methoxy)ethoxycarbonyl or(2-methoxy-1-methyl)ethoxycarbonyl. Alkenyloxycarbonyl is, for example,(C₃ -C₆)alkenyloxycarbonyl. Alkynyloxycarbonyl is, for example, (C₃-C₆)alkynyloxycarbonyl such as propargyloxycarbonyl,3-iodopropargyloxycarbonyl, 1-methylpropargyloxycarbonyl or3-butynyloxycarbonyl. Cydoalkoxycarbonyl is, for example, (C₃-C₆)cydoalkoxycarbonyl such as cydobutyloxycarbonyl,cydopentyloxycarbonyl or cydohexyloxycarbonyl. Cycloalkylalkoxycarbonylis, for example, (C₃ -C₆)cycloalkyl(C₁ -C₆)alkoxycarbonyl.(Alkenylthio)carbonyl is, for example, ((C₃ -C₆)alkenylthio)carbonyl.(Alkynylthio)carbonyl is, for example, ((C₃ -C₆)alkynylthio)Carbonyl.(Cycloalkylthio)carbonyl is, for example, ((C₃-C₆)cycloalkylthio)carbonyl. (Cycloalkylalkylthio)carbonyl is, forexample, ((C₃ -C₆)cycloalkyl(C₁ -C₆)alkylthio)carbonyl.Heterocydylalkoxycarbonyl is heterocydyl(C₁ -C₆)alkoxycarbonyl.Heterocydyloxycarbonyl is, for example, 3-tetrahydrofuryloxycarbonyl.Trialkylsilylalkoxycarbonyl is, for example, tri(C₁ -C₆)alkylsilyl(C₁-C₆)alkoxycarbonyl such as trimethylsilylmethoxycarbonyl.Dialkoxyphosphonylalkoxycarbonyl is, for example, di(C₁ -C₆)alkoxyphosphonyl(C₁ -C₆)alkoxycarbonyl such asdiethoxyphosphonylmethoxycarbonyl. Dialkyliminooxycarbonyl is, forexample, di(C₁ -C₆)alkyliminooxycarbonyl such asdimethyliminooxycarbonyl. Alkyliminooxycarbonyl is, for example, (C₁-C₆)alkyliminooxycarbonyl. Alkyl(alkoxy)iminooxycarbonyl is, forexample, (C₁ -C₆)alkyl((C₁ -C₆)alkoxy)iminooxycarbonyl.Alkyl(alkylthio)iminooxycarbonyl is, for example, (C₁ -C₆)alkyl((C₁-C₆)alkylthio)iminooxycarbonyl. Alkylaminocarbonyl is, for example,mono(C₁ -C₆)alkylaminocarbonyl such as isopropylaminocarbonyl or di(C₁-C₆)alkylaminocarbonyl. Alkenylaminocarbonyl is, for example, mono(C₃-C₆)alkenylaminocarbonyl. Alkynylaminocarbonyl is, for example, mono(C₃-C₆)alkynylaminocarbonyl such as propargylaminocarbonyl.Alkoxyaminocarbonyl is, for example, mono(C₁ -C₆)alkoxyaminocarbonylsuch as methoxyaminocarbonyl. Alkoxyalkyl is, for example, (C₁-C₆)alkoxy(C₁ -C₆)alkyl such as methoxymethyl, ethoxymethyl orisopropyloxymethyl. Alkenyloxyalkyl is, for example, (C₃-C₆)alkenyloxy(C₁ -C₆)alkyl. Alkynyloxyalkyl is, for example, (C₃-C₆)alkynyloxy(C₁ -C₆)alkyl such as propargyloxymethyl or1-methylpropargyloxymethyl. Cycloalkoxyalkyl is, for example, (C₃-C₆)cydoalkoxy(C₁ -C₆)alkyl. Cydoalkylalkoxyalkyl is, for example, (C₃-C₆)cycloalkyl(C₁ -C₆)alkoxy(C₁ -C₆)alkyl. Alkanoyloxyalkyl is, forexample, (C₁ -C₆)alkanoyloxy(C₁ -C₆)alkyl such as acetoxymethyl.Alkylthioalkyl is, for example, (C₁ -C₆)alkylthio(C₁ -C₆)alkyl such asmethylthiomethyl, isopropylthiomethyl or ethylthiomethyl.Alkenylthioalkyl is, for example, (C₃ -C₆)alkenylthio(C₁ -C₆)alkyl.Alkynylthioalkyl is, for example, (C₃ - C₆)alkynylthio(C₁ -C₆)alkyl.Cycloalkylthioalkyl is, for example, (C₃ -C₆)cycloalkylthio(C₁-C₆)alkyl. Cycloalkylalkylthioalkyl is, for example, (C₃-C₆)cycloalkyl(C₁ -C₆)alkylthio(C₁ -C₆)alkyl. (Alkanoylthio)alkyl is,for example, ((C₁ -C₆)alkanoylthio)(C₁ -C₆)alkyl. Phenoxyalkyl is, forexample, phenoxy(C₁ -C₆)alkyl such as phenoxymethyl. Phenylthioalkyl is,for example, phenylthio(C₁ -C₆)alkyl such as phenylthiomethyl.Alkoxycarbonylalkoxyalkyl is, for example, (C₁ -C₆)alkoxycarbonyl(C₁C₆)alkoxy(C₁ -C₆)alkyl such as ethoxycarbonyl(methyl)methoxymethyl.Alkylaminoalkyl is, for example, di(C₁ -C₆)alkylamino(C₁ -C₆)alkyl suchas dimethylaminoethyl. Alkenyl is, for example, (C₃ -C₆)alkenyl such asallyl. Alkynyl is, for example, (C₃ -C₆)alkynyl such as propargyl or1-methylpropargyl. Alkyloximyl is, for example, (C₁ -C₆)alkyloximyl suchas methyloximyl, isopropyloximyl or t-butyloximyl. Alkenyloximyl is, forexample, (C₃ -C₆)alkenyloximyl such as allyloximyl. Alkynyloximyl is,for example, (C₃ -C₆)alkynyloximyl such as propargyloximyl.Alkoxycarbonylalkyloximyl is, for example, (C₁ -C₆)alkoxycarbonyl(C₁-C₆)alkyloximyl. Phenylalkyloximyl is, for example, phenyl(C₁-C₆)alkyloximyl such as benzyloximyl. Alkyl(alkyl)oximyl is, forexample, (C₁ -C₆)alkyl((C₁ -C₆)alkyl)oximyl. Alkenyl(alkyl)oximyl is,for example, (C₃ -C₆)alkenyl((C₁ -C₆)alkyl)oximyl. Alkynyl(alkyl)oximylis, for example (C₃ -C₆)alkynyl((C₁ -C₆)alkyl)oximyl.Alkoxycarbonylalkyl(alkyl)oximyl is, for example, (C₁-C₆)alkoxycarbonyl(C₁ -C₆)alkyl((C₁ -C₆)alkyl)oximyl.Alkyl(alkoxy)oximyl is, for example, (C₁ -C₆)alkyl((C₁-C₆)alkoxy)oximyl. Alkenyl(alkoxy)oximyl is, for example, (C₃-C₆)alkenyl((C₁ - C₆)alkoxy)oximyl. Alkynyl(alkoxy)oximyl is, forexample, (C₃ -C₆)alkynyl((C₁ -C₆)alkoxy)oximyl.Alkoxycarbonylalkyl(alkoxy)oximyl is, for example, (C₁-C₆)alkoxycarbonyl(C₁ -C₆)alkyl((C₁ -C₆)alkoxy)oximyl.Alkyl(alkylthio)oximyl is, for example, (C₁ -C₆)alkyl((C₁-C₆)alkylthio)oximyl. Alkenyl(alkyltkio)oximyl is, for example, (C₃-C₆)alkenyl((C₁ -C₆)alkylthio)oximyl. Alkynyl(alkylthio)oximyl is, forexample, (C₃ -C₆)alkenyl((C₁ -C₆)alkylthio)oximyl.Alkoxycarbonylalkyl(alkylthio)oximyl is, for example, (C₁-C₆)alkoxycarbonyl(C₁ -C₆)alkyl((C₁ -C₆)alkylthio)oximyl. Alkylamino is,for example, mono(C₁ -C₆)alkylamino or di(C₁ -C₆)alkylamino.Alkenylamino is, for example, mono(C₃ -C₆)alkenylamino or di(C₃-C₆)alkenylamino. Alkynylamino is, for example, mono(C₃-C₆)alkynylamino. Alkanoylamino is, for example, mono(C₁-C₆)alkanoylamino such as acetamido. Alkoxycarbonylalkyl is, forexample, (C₁ -C₆)alkoxycarbonyl(C₁ -C₆)alkyl such asisopropyloxycarbonylmethyl. Cyanoalkyl is, for example, cyano(C₁-C₆)alkyl such as cyanomethyl or 1-cyanoethyl. Phenylalkyl is, forexample, phenyl(C₁ -C₆)alkyl such as benzyl. Heterocyclylalkyl is, forexample, heterocydyl(C₁ -C₆)alkyl such as epoxymethyl or2-tetrahydrofuranylmethyl. Heterocyclylcarbonyl is, for example,isoxazolidinylcarbonyl. Heterocyclylalkoxy is, for example,heterocydyl(C₁ -C₆)alkoxy such as epoxymethoxy, 2-pyridylmethoxy or2-tetrahydrofuranylmethoxy. teterocyclyloxy is, for example,3-tetrahydrofuranyloxy.

In a preferred embodiment of the invention are compounds of the formula##STR4## wherein

A is C═O, C═S or CH₂ ;

A¹ is C═O or CH₂ ;

provided when Z is hydrogen, A and A¹ are not both CH₂ ;

D is CH or, when X is H, N;

Q is (CH₂)_(n), where n is 0 or 1, or oxygen;

R is (C₁ -C₄)alkyl, (C₁ -C₄)haloalkyl or phenyl;

R¹ is H or (C₁ -C₂)alkyl, provided R¹ is H when X and Z areindependently hydrogen or halogen and Y is halogen;

R² is H or, together with R and R¹, fused phenyl;

X is H, Cl, Br, CN or F;

Y is H, Cl, Br, F, I, CH₃, SCH₃, nitro, or OCH₃ ;

provided when Y is hydrogen, R is trifluoromethyl, R¹ and R² arehydrogen and Z is not hydrogen;

T is H or F;

Z is H; OH; halogen; CN; SH; (C₁ -C₆)alkyl; (C₁ -C₆)haloalkyl; --OSO₂(C₁ -C₆)alkyl; --OSO₂ phenyl; carboxy; formyl; phenoxycarbonyl; (C₁-C₆)alkoxy; (C₃ -C₆)alkenyloxy; (C₃ -C₆)alkynyloxy; cyano(C₁ -C₆)alkoxy;phenyl(C₁ -C₆)alkoxy; (C₁ -C₆)alkylthio; (C₁ -C₆)alkanoyloxy; (C₁ -C₆)alkanoylthio; (C₁ -C₆)alkoxycarbonyl(C₁ -C₄)alkylthio; (C₁-C₆)alkoxycarbonyl(C₁ -C₄)alkoxy; (C₁ -C₆)alkoxycarbonyl((C₁-C₆)alkoxy)(C₁ -C₆)alkoxy; (C₁ -C₆)alkoxy(C₁ C₆)alkoxy; (phenylthio)(C₁-C₆)alkoxy; carboxy(C₁ -C₆)alkoxy; heterocycyloxy; heterocydyl(C₁-C₆)alkoxy; (C₁ -C₆)alkylcarbonyl; (C₁ -C₆)alkoxycarbonyl; ((C₁-C₆)alkylthio)carbonyl; (C₁ -C₆)alkoxycarbonyl (C₁ -C₆)alkoxycarbonyl;(C₁ l-C₆)alkoxy(C₁ -C₆)alkoxycarbonyl; cyano(C₁ -C₆)alkoxycarbonyl; (C₃-C₆)alkenyloxycarbonyl; (C₃ -C₆)alkynyloxycarbonyl; halo(C₃-C₆)alkynyloxycarbonyl; (C₃ -C₆)cycloalkoxycarbonyl;heterocydylcarbonyl; heterocydyloxycarbonyl; tri(C₁ -C₆)alkylsilyl(C₁-C₆)alkoxycarbonyl; di(C₁ -C₆)alkoxyphosphonyl(C₁ -C₆)alkoxycarbonyl;di(C₁ -C₆)alkyliminooxycarbonyl; mono(C₁ -C₆)alkylaminocarbonyl; mono(C₃-C₆)alkynylaminocarbonyl; phenylaminocarbonyl; mono(C₁-C₆)alkoxyaminocarbonyl; (C₁ -C₆)alkoxy(C₁ -C.sub. 6)alkyl; (C₃-C₆)alkenyloxy(C₁ -C₆)alkyl; (C₃ -C₆)alkynyloxy(C₁ -C₆)alkyl; (C₁-C₆)alkanoyloxy(C₁ -C₆)alkyl; (C₁ -C₆)alkylthio(C₁ -C₆)alkyl; phenoxy(C₁-C₆)alkyl; phenylthio(C₁ -C₆)alkyl; (C₁ -C₆)alkoxycarbonyl(C₁-C₆)alkoxy(C₁ -C₆)alkyl; (C₁ -C₆)alkyloximyl; (C₃ -C₆)alkenyloximyl; (C₃-C₆)alkynyloximyl; phenyl(C₁ -C₆)alkyloximyl; heterocyclyl; mono(C₁-C₆)alkanoylamino; or

Z and Y together form a 5- or 6-membered heterocyclic ring fused to thephenyl ring structure to form a bicyclic moiety having the structure##STR5## wherein

L is oxygen or sulfur;

R³ is hydrogen or (C₁ -C₃)alkyl; and

R⁴ is hydrogen; (C₁ -C₈)alkyl; (C₃ -C₆)alkenyl; (C₃ -C₆)alkynyl; C₁-C₆)alkoxy(C₁ -C₆)alkyl; (C₃ -C₆)cycloalkyl; (C₃ -C₆)cycloalkyl(C₁`C₆)alkyl; (C₁ -C₆)alkylthio(C₁ -C₆)alkyl; phenyl(C₁ -C₆)alkyl; cyano(C₁-C₆)alkyl; (C₁ -C₆)alkoxycarbonyl(C₁ -C₆)alkyl; (C₁ -C₆)alkoxycarbonyl;heterocyclyl; heterocydyl(C₁ -C₆)alkyl; di(C₁ -C₆)alkylamino(C₁-C₆)alkyl; di(C₁ -C₆)alkylaminocarbonyl(C₁ -C₆)alkyl; or (C₁-C₆)alkanoyl.

In one class of the preferred embodiment of the invention are ether andthioether glutarimides of Formula I wherein

A is C═O or CH₂ ;

A¹ is C═O or CH₂ ;

D is CH or, when X is H, N;

Q is (CH₂)_(n), where n is 0 or 1;

R is (C₁ -C₄)alkyl, (C₁ -C₄)haloalkyl or phenyl;

R¹ is H or (C₁ -C₂)alkyl;

R² is H or, together with R and R¹, fused phenyl;

X is H, Cl, Br or F;

Y is H, Cl, Br, F or CH₃ ;

T is H or F; and

Z is (C₁ -C₆)alkoxy; (C₃ -C₆)alkenyloxy; (C₃ -C₆)alkynyloxy; phenyl(C₁-C₆)alkoxy; (C₁ -C₆)alkylthio; (C₁ -C₆)alkanoyloxy; (C₁-C₆)alkanoylthio; (C₁ -C₆)alkoxycarbonyl(C₁ -C₄)alkylthio; (C₁-C₆)alkoxycarbonyl(C₁ -C₄)alkoxy; cyano(C₁ -C₆)alkoxy; (C₁ -C₆)alkoxy(C₁-C₆)alkoxy; (phenylthio)(C₁ -C₆)alkoxy; carboxy(C₁ -C₆)alkoxy;heterocyclyloxy; heterocyclyl(C₁ -C₆)alkoxy; (C₃ -C₆)cydoalkoxy; (C₃-C₆)cycloalkyl(C₁ -C₆)alkoxy; or (C₁ -C₆)alkoxycarbonyl (C₁-C₆)alkoxy!(C₁ -C₆)alkoxy.

Preferred compounds of these ether and thioether glutarimides arecompounds of Formula I wherein A and A¹ are C═O; D is CH; Q is (CH₂)_(n); n is 0; R is CH₃, CH₂ or CF₃ ; R¹ is H; R² is H; X is Cl or F; Y isBr, F, or Cl; T is H; and Z is (C₁ -C₆)alkoxy, (C₃ -C₆)alkenyloxy, (C₃-C₆)alkynyloxy, (C₃ -C₆)cydoalkoxy, (C₃ -C₆)cycloalkyl(C₁ -C₆)alkoxy or(C₁ -C₆)alkyloxy(C₁ -C₆)alkyloxy.

More preferably when R is CF₃, R¹ and R² are hydrogen, X is fluoro, andY is chloro, Z is allyloxy, isopropyloxy, s-butyloxy, propargyloxy,1-methylpropargyloxy, cyclopentyloxy, cyclopropylmethoxy,3-tetrahydrofuranyloxy, or methoxymethoxy.

More preferably when R is CHF₂, R¹ and R² are hydrogen, X is fluoro andY is chloro, Z is propargyloxy.

More preferably when R is CF₃, R¹ and R² are hydrogen, X is fluoro, andY is bromo, X is propargyloxy.

In a second class of the preferred embodiment of the invention are esterglutarimides of Formula I wherein

A is C═O or CH₂ ;

A¹ is C═O or CH₂ ;

D is CH or, when X is H, N;

Q is (CH₂)_(n), where n is 0 or 1;

R is (C₁ -C₄)alkyl, (C₁ -C₄)haloalkyl or phenyl;

R¹ is H or (C₁ -C₂)alkyl;

R² is H or, together with R and R¹, fused phenyl;

X is H, Cl, Br or F;

Y is H, Cl, Br, F or CH₃ ;

T is H or F;

Z is carboxy; formyl; (C₁ -C₆)alkoxycarbonyl; (C₁ -C₆)alkoxycarbonyl(C₁-C₆)alkoxycarbonyl; cyano(C₁ -C₆)alkoxycarbonyl; (C₁ -C₆)alkoxy(C₁-C₆)alkoxycarbonyl; ((C₁ -C₆)alkylthio)carbonyl; (C₁ -C₆)alkylcarbonyl;(C₃ -C₆)alkenyloxycarbonyl; halo(C₃ -C₆)alkynyloxycarbonyl; (C₃-C₆)alkynyloxycarbonyl; (C₃ -C₆)cydoalkoxycarbonyl;heterocylyloxycarbonyl; tri(C₁ -C₆ )alkylsilyl(C₁ -C₆)alkoxycarbonyl;di(C₁ -C₆)alkoxyphosphonyl(C₁ -C₆)alkoxycarbonyl; di(C₁-C₆)alkyliminooxycarbonyl; monoalkylaminocarbonyl; mono(C₁-C₆)alkoxyaminocarbonyl; mono(C₃ -C₆)alkynylaminocarbonyl; orphenylaminocarbonyl.

Preferred compounds of these ester glutarimides are compounds wherein Aand A¹ are C═O; D is CH; Q is (CH₂)_(n) ; n is 0; R is CH₃, CHF₂ or CF₃; R¹ is H; R² is H; X is Cl or F; Y is Br, F, or Cl; T is H; and Z isCO₂ H, (C₁ -C₆)alkoxycarbonyl, (C₃ -C₆)cydoalkoxycarbonyl, (C₃-C₆)alkenyloxycarbonyl or (C₃ -C₆)alkynyloxycarbonyl.

More preferably when R is CF₃, R¹ and R² are hydrogen, X is fluoro, andY is chloro, Z is carboxy, methoxycarbonyl, n-propyloxycarbonyl,isopropyloxycarbonyl, s-butyloxycarbonyl, cyclobutyloxycarbonyl orethoxycarbonyl.

More preferably when R is CF₃, R¹ and R² are hydrogen, X is fluoro, andY is bromo, Z is isopropyloxycarbonyl.

More preferably when R is CHF₂, R¹ and R² are hydrogen, X is fluoro, andY is chloro, Z is isopropyloxycarbonyl.

More preferably when R is CH₃, R¹ and R² are hydrogen, X is fluoro, andY is chloro, Z is isopropyloxycarbonyl.

In a third class of the preferred embodiment of the invention are alkyland oximyl glutarimides of Formula I wherein

A is C═O or CH₂ ;

A¹ is C═O or CH₂ ;

D is CH or, when X is H, N;

Q is (CH₂)_(n), where n is 0 or 1;

R is (C₁ -C₄)alkyl, (C₁ -C₄)haloalkyl or phenyl;

R¹ is H or (C₁ -C₂)alkyl;

R² is H or, together with R and R¹, fused phenyl;

X is H, Cl, Br or F;

Y is H, Cl, Br, F or CH₃ ;

T is H or F;

Z is (C₁ -C₆)alkyl; (C₁ -C₆)alkoxy(C₁ -C₆)alkyl; (C₃ -C₆)alkenyloxy(C₁-C₆)alkyl; (C₃ -C₆)alkynyloxy(C₁ -C₆)alkyl; (C₁ -C₆)alkanoyloxy(C₁-C₆)alkyl; ((C₁ -C₆)alkylthio)(C₁ -C₆)alkyl; phenoxy(C₁ -C₆)alkyl;phenylthio(C₁ -C₆)alkyl; (C₁ -C₆)alkoxycarbonyl(C₁ -C₆)alkoxy(C₁-C₆)alkyl; (C₁ -C₆)alkyloximyl; (C₃ -C₆)alkenyloximyl; (C₂-C₆)alkynyloximyl; or phenyl(C₁ -C₆)alkyloximyl.

Preferred compounds of this class of alkyl and oximyl glutarimides arecompounds wherein A and A¹ are C═O; D is CH; Q is (CH₂)_(n) ; n is 0; Ris CH₃, CHF₂ or CF₃ ; R¹ is H; R² is H; X is Cl or F; Y is Br, F, or Cl;T is H; and Z is (C₁ -C₆)alkyl, (C₁ -C₆)alkoxymethyl, (C₃-C₆)alkenyloxymethyl, (C₃ -C₆)alkynyloxymethyl, (C₁ -C₆)alkyloximyl or(C₃ -C₆)alkynyloximyl.

More preferably R is CF₃, R¹ and R² are hydrogen, X is fluoro, Y ischloro and Z is isopropyloxymethyl, 1-methylpropargyloxymethyl,methyloximyl, isopropyloximyl, propargyloximyl or t-butyloximyl.

In yet a fourth class of the preferred embodiment of the invention areheterocyclic glutarimides of Formula I wherein Z and Y form aheterocyclic ring of the formula ##STR6## wherein

A and A¹ are C═O;

D is CH;

Q is (CH₂)_(n), where n is 0;

L is O or S;

X is H or F;

R is (C₁ -C₄)alkyl, (C₁ -C₄)haloalkyl or phenyl;

R¹ is H or (C₁ -C₂)alkyl;

R² is H or, together with R and R¹, fused phenyl;

R³ is H or (C₁ -C₃)alkyl; and

R⁴ is hydrogen, (C₁ -C₈)alkyl, (C₃ -C₆)alkenyl, (C₃ -C₆)alkynyl, (C₁-C₆)alkoxy(C₁ -C₆)alkyl, (C₁ -C₆)alkylthio(C₁ -C₆)alkyl, (C₃-C₆)cycloalkyl, (C₃ -C₆)cycloalkyl(C₁ -C₆)alkyl, phenyl(C₁ -C₆)alkyl,cyano(C₁ -C₆)alkyl, (C₁ -C₆)alkoxycarbonyl(C₁ -C₆)alkyl, heterocyclyl,heterocydyl(C₁ -C₆)alkyl, di(C₁ -C₆)alkylamino(C₁ -C₆)alkyl, di(C₁-C₆)alkylaminocarbonyl(C₁ -C₆)alkyl, (C₁ -C₆)alkoxycarbonyl or (C₁-C₆)alkanoyl.

Preferred compounds of this class of the preferred embodiment arecompounds of the formula ##STR7## wherein

L is O or S;

X is H or F;

R is CH₃, CHF₂ or CF₃ ;

R³ is H or (C₁ -C₃)alkyl; and

R⁴ is hydrogen, (C₁ -C₆)alkyl, (C₃ -C₆)alkenyl, halo(C₃ -C₆)alkenyl, (C₃-C₆)alkynyl, (C₃ -C₆)cycloalkyl, (C₃ -C₆)cycloalkyl(C₁ -C₆)alkyl, (C₁-C₆)alkoxymethyl, (C₁ -C₆)alkylthiomethyl, cyano(C₁ -C₆)alkyl,heterocydyl, heterocydyl(C₁ -C₆)alkyl, di(C₁ -C₆)alkylamino(C₁ -C₆)alkylor di(C₁ -C₆)alkylaminocarbonyl(C₁ -C₆)alkyl.

More preferably X is H or F, R is CH₃ CHF₂ or CF₃, R³ is H, CH₃ or CH₂CH₃ and R⁴ is propargyl, allyl, ethoxymethyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, s-butyl, 1-ethylpropyl, 2-methoxyethyl,methoxymethyl, methylthiomethyl, 1-cyanoethyl, 1-methylpropargyl,2-methylallyl, cyanomethyl, cyclopropylmethyl, cyclopentyl,dimethylaminocarbonylmethyl, 2-tetrahydrofuranylmethyl,3-tetrahydrofuranyl, 2-chloroallyl, or 3,3-dichloroallyl.

Most preferably when R is CH₃, R³ is H, L is oxygen and R⁴ is propargyl,X is F.

Most preferably when R is CF₃, R³ is CH₃, L is oxygen and R⁴ ispropargyl, X is H or F.

Most preferably when R is CF₃, R³ and X are H, and L is oxygen, R⁴ ispropargyl, n-propyl, 1-methylpropargyl, allyl, s-butyl, methoxymethyl or2-methoxyethyl.

Most preferably when R is CF₃, R³ is H, L is oxygen and X is F, R⁴ ispropargyl, cyanomethyl, allyl, methoxymethyl, ethoxymethyl, n-propyl,isopropyl, n-butyl, isobutyl, s-butyl, 1-cyanoethyl, 2-methylallyl,methylthiomethyl, 2-ethylpropyl, cyclopropylmethyl, cyclopentyl,dimethylaminocarbonylmethyl, 2-tetrahydrofuranylmethyl,3-tetrahydrofuranyl, 2-chloroallyl, 3,3-dichloroallyl or ethyl.

Most preferably when R is CFH₂, R³ is H, L is oxygen and X is F, R⁴ isallyl.

Most preferably when R is CF₃, R³ is CH₂ CH₃, L is oxygen and X is F, R⁴is propargyl.

Most preferably when R is CF₃, R³ is H, L is sulfur and X is F, R⁴ ispropargyl.

Other preferred compounds of this class of the preferred embodiment arecompounds of the formula ##STR8## wherein R is CF₃ or CH₃, X is H or Fand R⁴ is (C₁ -C₆)alkyl.

Most preferably, R is CF₃, X is F, and X is n-propyl.

The glutarimides of the instant invention can be prepared by a two-stepsequence starting from an anilino or amino compound of the formula##STR9## wherein D, T, X, Y, Z and Q are as defined in Formula I above.

Compound II is reacted with about an equivalent of a suitablysubstituted glutaric anhydride having the formula ##STR10##

wherein R, R¹ and R² are as defined in Formula I above, to yield acompound having the formula ##STR11## Examples of suitable solvents forthis reaction include ethers, such as ethyl ether, tetrahydrofuran (THF)and glyme; hydrocarbons, such as toluene; acetonitrile;N,N-dialkylamides, such as dimethylformamide; and halocarbons such asmethylene chloride and chloroform. A mixture of solvents can be used toachieve homogeniety. The reaction is generally carried out at aboutatmospheric pressure at a temperature of from about -10° C. to about100° C. Preferably the temperature employed is in the range of fromabout 0° C. to about 70° C.

The compound of Formula IV is then cyclized in the presence of aceticanhydride and sodium acetate, or acetyl chloride, or ethyl acetate withthionyl chloride and N,N-dimethylformamide to obtain the desiredN-substituted glutarimide (Formula V) of the instant invention. Thereaction is generally carried out at a temperature of from about -10° C.to about 250° C. More preferably the reaction is carried out at atemperature of from about 30° C. to about 150° C.

The N-substituted glutarimide of Formula V, ##STR12## wherein Q is notoxygen, can be converted to the thioglutarimide of the invention(Formula VI), ##STR13## for example, by use of a thiocarbonyl conversionagent such as Lawson's reagent(2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide) orphosphors pentasulfide in the presence of hexmethylphosphoride orxylenes. The reaction is generally carried out at a temperature of fromabout -10° C. to about 250° C., preferably from about 50° C. to about150° C.

The N-substituted glutarimide V (wherein Q is not oxygen) can also bereduced to the corresponding N-substituted piperidine of the invention(Formula VII) ##STR14## using, for example, a reducing agent such aslithium aluminum hydride. The reaction is generally carried out in anaprotic solvent such as ethyl ether or tetrahydrofuran. The reaction isgenerally carried out at a temperature range from about -20° C. to about100° C. Preferably the temperature is from about 0° C. to about 65° C.

The piperidones of the invention (Formula VIII) ##STR15## can beprepared by a three step sequence starting from the compound of FormulaIV (wherein Q is not oxygen). The glutaramic acid of Formula IV is firstreduced to the analogous 5-hydroxypentanamide. For example, a reducingagent such as borane-methyl sulfide complex in a solvent such astetrahydrofuran or ethyl ether is used. The temperature range is fromabout -20° C. to about 150° C., preferably from about O° C. to about100° C.

The 5-hydroxypentanamide is converted to the corresponding5-chloropentanamide, for example, by reacting the hydroxy compound withthionyl chloride in an aprotic solvent such as methylene chloride at atemperature range from about -20° C. to about 150° C., preferably fromabout 0° C. to about 100° C.

The 5-chloropentanamide is then cyclized to the piperidone of FormulaVIII, for example, by treatment with base, such as sodium hydroxide inan aprotic solvent such as tetrahydrofuran at a temperature range fromabout -20° C. to about 150° C., preferably from about 0° C. to about100° C.

In the case where Z is a substituted carbonyl moiety, the carboxylicacid of Formula V (Z═CO₂ H, wherein Q is not oxygen) can be converted tothe corresponding acid chloride (Z═C(O)Cl) by reaction with achlorinating agent, for example thionyl chloride, in an inert solvent,preferably a hydrocarbon such as toluene or chloroform, at a temperaturerange between -20° C. and 200° C., preferably from about 50° C. to about100° C. The acid halide is then reacted with the appropriate nucleophile(for example, alcohol, alkyl mercaptan, amine) in the presence of asuitable base, preferably triethylamine or pyridine, to yield thecorresponding compound of Formula I. The reaction is carried out in aninert organic solvent, preferably THF or methylene chloride.

In the case where Y and Z together form a heterocyclic ring, theamino-substituted heterocycle is prepared by means known in the art andthen reacted with the requisite glutaric anhydride (III) as describedabove. Alternatively, when the heterocycle contains a site which can bealkylated, the alkylation can be carried out after the reaction withglutaric anhydride and subsequent cyclization has taken place.

In some cases where Z is a substituted alkoxy moiety, the phenol ofFormula V (Z═OH, when Q is not oxygen) is treated with anon-nucleophilic base such as sodium hydride and reacted with anappropriate alkylating agent to yield the corresponding glutarimide. Thereaction is carried out in an inert organic solvent, for example,tetrahydrofuran or ethyl ether at a temperature range from about -20° C.to about 150° C., preferably from about 0° C. to about 100° C.

In the case where Z is an oximyl moiety, the benzaldehyde of Formula V(Z═CHO, when Q is not oxygen) is reacted with the appropriatealkoxyamine or alkoxyamine salt in a polar organic solvent such asethanol at a temperature range from about -20° C. to about 150° C.,preferably from about 0° C. to about 100° C. When a salt is used, a basesuch as pyridine may be added to the reaction mixture.

The starting glutaric anhydrides are prepared as is known in the art,for example, in J. Gootjes and W. Th. Nanto, Rec. Trav. Chem, 80, 1183(1965). Alternatively, ethyl 4,4,4-trifluorocrotonate and sodio diethylmalonate are reacted in the presence of a catalytic amount of a catalystsuch as tetrabutylammonium bromide to yield ethyl2-(trifluoromethyl)propanetrioate which is in turn treated with a strongbase such as potassium hydroxide, preferably between about 50° C. andabout 150° C., then acidified and decarboxylated to yield3-(trifluoromethyl)glutaric acid.

The starting anilino and amino are prepared by known methods, asdisclosed for example, in U.S. Pat. Nos. 4,439,229, 4,484,940,4,484,941, 4,594,099, and 4,640,707, and in PCT/EP87/00279 andPCT/US87/00056 and in the references cited therein.

The following examples will further illustrate this invention but arenot intended to limit it in any way. In Tables I to IV examples ofN-substituted glutarimides are listed with their melting points, whenobtained. The proton NMR data are listed in Table V for those compoundsfor which no melting point is supplied. Specific illustrativepreparations of the compounds are described after Table V.

                                      TABLE I    __________________________________________________________________________     ##STR16##    No. R, R.sup.1               X  Y    Z             m.p. (°C.)    __________________________________________________________________________     1. CF.sub.3, H               F  Cl   OCH.sub.3     55-70     2. CF.sub.3, H               F  Cl   OCH.sub.2 CH.sub.3                                     72-75     3. CF.sub.3, H               F  Cl   OCH.sub.2 CH.sub.2 CH.sub.3                                     106-110     4. CF.sub.3, H               F  Cl   OCH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3                                     112-114     5. CF.sub.3, H               F  Cl   OCH(CH.sub.3).sub.2                                     88-90     6. CF.sub.3, H               F  Cl   OCH(CH.sub.3)CH.sub.2 CH.sub.3                                     oil     7. CF.sub.3, H               F  Cl   OCH.sub.2 CH(CH.sub.3).sub.2                                     124-127     8. CF.sub.3, H               F  Cl   OCOCH.sub.3   71-76     9. CF.sub.3, H               F  Cl   OCH.sub.2 CHCH.sub.2                                     80-83     10.        CF.sub.3, H               F  Cl   OCH.sub.2 CCH 88-91     11.        CF.sub.3, H               F  Cl   OCH.sub.2 CN  123.5-127     12.        CF.sub.3, H               F  Cl   OCH.sub.2 OCH.sub.3                                     oil     13.        CF.sub.3, H               F  Cl   OSO.sub.2 C.sub.6 H.sub.5                                     214-215     17.        CF.sub.3, H               F  Br   H             140-143     18.        CF.sub.3, H               F  F    H             108-113     19.        CF.sub.3, H               F  Cl   OH            112-114     20.        CF.sub.3, H               H  Cl   Cl            44-46     21.        CF.sub.3, H               H  Br   CF.sub.3      99-102     22.        CF.sub.3, H               H  Br   H             163-164     23.        CF.sub.3, H               H  CH.sub.3                       H             179-182     24.        CF.sub.3, H               H  Cl   OCH.sub.2 CCH 155-156     25.        CF.sub.3, H               Cl Cl   OCH.sub.2 CCH oil     29.        CH.sub.3, H               F  Cl   OCH.sub.2 CCH 130-133     30.        CH.sub.3, H               F  Cl   OCH(CH.sub.3).sub.2                                     104-107     31.        CH.sub.3, H               Cl Cl   OCH.sub.2 CCH 170-175     32.        CH.sub.3, H               H  Cl   OCH.sub.2 CCH 171-174     33.        CF.sub.3, H               F  H    CO.sub.2 CH(CH.sub.3).sub.2                                     146-148     34.        CH.sub.3, H               F  Br   H             99-101     38.        CH.sub.3, CH.sub.3               F  Cl   OCH.sub.2 CCH 101-102.5     39.        CF.sub.3, H               CN Cl   H             135-138     40.        CF.sub.3, H               H  SCH.sub.3                       H             144-145.5     41.        CF.sub.3, H               F  Cl   SCH(CH.sub.3).sub.2                                     oil     42.        CH.sub.3, H               F  Cl   OCOCH.sub.3   135-141     43.        CH.sub.2 CH.sub.3, H               F  Cl   OCH.sub.2 C CH                                     102-107     44.        CH.sub.2 CH.sub.3, H               F  Cl   OCH(CH.sub.3).sub.2                                     81-84     45.        CF.sub.2 CF.sub.3, H               F  Cl   OCH.sub.2 CCH 131-132     46.        CF.sub.2 CF.sub.3, H               F  Cl   OCH(CH.sub.3).sub.2                                     66-67.5     47.        CH(CH.sub.3).sub.2, H               F  Cl   OCH.sub.2 CCH 103-106     48.        CH(CH.sub.3).sub.2, H               F  Cl   OCH(CH.sub.3).sub.2                                     oil     49.        C.sub.6 H.sub.5, H               F  Cl   OCH.sub.2 CCH 188-190     50.        CF.sub.3, H               F  Cl   SCH.sub.2 CO.sub.2 CH(CH.sub.3).sub.2                                     oil     51.        CF.sub.3, H               F  Cl   CO.sub.2 CH(CH.sub.3).sub.2                                     96-98     52.        CF.sub.3, H               F  Cl   OCH.sub.2 SC.sub.6 H.sub.5                                     108-109.5     53.        CF.sub.3, H               F  Cl   OCH(CH.sub.3)CN                                     175-177(dec)     54.        CF.sub.3, H               F  Cl   OCH.sub.2 CO.sub.2 CH.sub.3                                     90-91     55.        CF.sub.3, H               F  Cl   OCH(OCH.sub.3)CO.sub.2 CH.sub.3                                     40.5-43     56.        CF.sub.3, H               F  Cl   SCH.sub.2 CO.sub.2 CH.sub.3                                     oil     57.        CF.sub.3, H               F  Cl   SCH.sub.2 CO.sub.2 H                                     137-139     58.        CF.sub.3, H               F  Cl   SH            68-72     59.        CF.sub.3, H               F  Cl   SCOCH.sub.3   oil     60.        CF.sub.3, H               F  Cl   SCH.sub.3     114-116     61.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.3                                     172-174     62.        CF.sub.3, H               F  Cl   CO.sub.2 H    220-225     63.        CH.sub.2 CH.sub.3, H               H  Br   H             140-145     66.        CH.sub.3, H               H  F    H             125-127     67.        CH.sub.3, H               H  Cl   H             163-164     68.        CH.sub.3, H               H  I    H             174-177     69.        CH.sub.3, H               H  OCH.sub.3                       H             112-113     70.        CH.sub.3, H               H  Cl   Cl            156-159     71.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 CH.sub.3                                     104- 105     72.        CF.sub.3, H               F  Cl   CO.sub.2 (CH.sub.2).sub.2 CH.sub.3                                     79-80     73.        CF.sub.3, H               F  Cl   OCH.sub.2 C.sub.6 H.sub.5                                     121-122.5     74.        CF.sub.3, H               F  Cl   CO.sub.2 CH(CH.sub.3)CO.sub.2 CH.sub.3                                     94-96     75.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 CH(CH.sub.3).sub.2                                     82-85     76.        CF.sub.3, H               F  Cl   OCH.sub.2 CCCH.sub.3                                     95-97     77.        CF.sub.3, H               F  Cl   CONHC.sub.6 H.sub.5                                     55-60     78.        CF.sub.3, H               F  Cl   CONHCH(CH.sub.3).sub.2                                     95-112     79.        CF.sub.3, H               F  Cl   CH.sub.2 OCOCH.sub.3                                     115-116.5     80.        CF.sub.3, H               Cl Cl   CO.sub.2 CH(CH.sub.3).sub.2                                     oil     81.        CF.sub.3, H               F  Cl   CH.sub.2 OCH.sub.3                                     86-88     82.        CF.sub.3, H               F  Cl   CH.sub.2 OCH(CH.sub.3).sub.2                                     77-79     83.        CF.sub.3, H               F  Cl   CH.sub.2 OCH.sub.2 C CH                                     oil     92.        CF.sub.3 , H               F  Cl   CH.sub.3      119-120     93.        CF.sub.3, H               F  Cl   CHNOCH.sub.3  150.5-152.5     94.        CF.sub.3, H               F  Cl   CHO           146-148.5     95.        CF.sub.3, H               F  Cl   COCH.sub.3    127-129     99.        CF.sub.3, H               H  H    OCH.sub.2 CCH 70.5-72    100.        CF.sub.3, H               F  Cl   CO.sub.2 NC(CH.sub.3).sub.2                                     144-145    101.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 PO(OC.sub.2 H.sub.5).sub.2                                     oil    102.        CF.sub.3, H               F  Cl   COSC.sub.2 H.sub.5                                     102-104    103.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 CO.sub.2 C.sub.2 H.sub.5                                     139-140    104.        CF.sub.3, H               F  Cl   COSCH(CH.sub.3).sub.2                                     102-105    106.        CF.sub.3, H               F  Cl   CH.sub.2 SCH(CH.sub.3).sub.2                                     107-109    107.        CF.sub.3, H               F  Cl   CH.sub.2 SC.sub.2 H.sub.5                                     oil    108.        CF.sub.3, H               F  Cl   CH.sub.2 OC.sub.6 H.sub.5                                     120-122    109.        CF.sub.3, H               F  Cl   CH.sub.2 SC.sub.6 H.sub.5                                     oil    110.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 CCH                                     120-123    111.        CF.sub.3, H               F  Cl   CO.sub.2 CH(CH.sub.3)CCH                                     45-50    112.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 CH.sub.2 CCH                                     oil    113.        CF.sub.3, H               F  Cl   CO.sub.2 CH(CH.sub.3)CN                                     oil    114.        CF.sub.3, H               F  Cl   CONHOCH.sub.3 158-162    115.        CF.sub.3, H               F  Cl   CH.sub.2 OCH(CH.sub.3)CO.sub.2 C.sub.2 H.sub.5                                     oil    116.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 CH.sub.2 OCH.sub.3                                     oil    117.        CF.sub.3, H               F  Cl   CO.sub.2 CH(CH.sub.3)CH.sub.2 OCH.sub.3                                     oil    118.        CF.sub.3, H               F  Cl   CO.sub.2 CH(CH.sub.3)CH.sub.2 CH.sub.3                                     oil    127.        CF.sub.3, H               F  Cl                        ##STR17##    77-78    130.        CF.sub.3, H               F  Cl                        ##STR18##    52-55    133.        CF.sub.3, H               F  Cl   CONHC(CH.sub.3).sub.2 CCH                                     166-170    135.        CF.sub.3, H               F  Cl                        ##STR19##    oil    140.        CF.sub.3, H               F  Cl   OCH.sub.2 CH.sub.2 CCH                                     89-91    141.        CF.sub.3, H               F  C2   OCH(CH.sub.3)CCH                                     102-104    144.        CF.sub.3, H               F  Cl   CH.sub.2 OCH(CH.sub.3)CCH                                     oil    148.        CF.sub.3, H               F  OCH.sub.3                       NHCOCH.sub.3  155-157    150.        CF.sub.3, H               F  Cl   CHNOCH.sub.2 CHCH.sub.2                                     oil    152.        CF.sub.3, H               F  CN   H             154-155    156.        CF.sub.3, H               F  Cl   CHNOCH.sub.2 C.sub.6 H.sub.5                                     187-188    158.        CF.sub.3, H               F  Cl   CHNOC.sub.2 H.sub.5                                     111.5-113.5    159.        CF.sub.3, H               F  Cl   CHNOH         75-80(subl**)    160.        CF.sub.3, H               F  Cl   OCH.sub.2 CH.sub.2 OCH.sub.3                                     95-97    161.        CF.sub.3, H               F  Cl   CO.sub.2 C.sub.6 H.sub.5                                     206-208    162.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 Si(CH.sub.3)3                                     95-98    163.        CF.sub.3, H               F  Cl                        ##STR20##    53-55    164.        CF.sub.3, H               F  Cl   CONHCH.sub.2 CCH                                     63-65    168.        CF.sub.3, H               F  Cl   CHNOC(CH.sub.3)3                                     140-141.5    169.        CF.sub.3, H               F  Cl   CN            210-212    172.        CF.sub.3, H               F  Cl   C(CH.sub.3)NOCH.sub.3                                     130-135    173.        CF.sub.3, H               F  Cl   C(CH.sub.3)NOH                                     178-179.5    174.        CF.sub.3, H               F  Cl   C(CH.sub.3)NOCH.sub.2 CH.sub.3                                     106-109    175.        CF.sub.3, H               F  Cl   C(CH.sub.3)NOC(CH.sub.3)3                                     132-134    176.        CF.sub.3, H               F  Cl   C(CH.sub.3)NOCH.sub.2 CHCH.sub. 2                                     95.5-98    177.        CF.sub.3, H               F  Cl   CO.sub.2.sup.- NH.sub.3 CH(CH.sub.3).sub.2.sup.+                                     168-173 dec    178.        CF.sub.3, H               F  Cl   C(CH.sub.3)NOCH.sub.2 C.sub.6 H.sub.5                                     92-97    180.        CF.sub.3, H               H  OCF.sub.3                       H             113-116    183.        CF.sub.3, H               H  Cl   N(CH.sub.3)C(O)CH.sub.3                                     203-204    185.        CF.sub.3, H               H  NO.sub.2                       H             133-134    186.        CF.sub.3, H               F  Cl   CHNOCH(CH.sub.3).sub.2                                     140-141.5    187.        CF.sub.3, H               F  Cl   CHNOCH.sub.2 CCH                                     57-61    190.        CF.sub.3, H               F  Cl   OSO.sub.2 CH.sub.2 CH.sub.3                                     41-44    191.        CF.sub.3, H               H  CF.sub.3                       H             143-144    192.        CF.sub.3, H               F  Cl                        ##STR21##    63-65.5    193.        CF.sub.3, H               F  Cl                        ##STR22##    157-159    194.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub. 2 C.sub.6 H.sub.5                                     50-55    195.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 CHCH.sub.2                                     107-108    196.        CF.sub.3, H               F  Cl                        ##STR23##    91-92    197.        CF.sub.3, H               F  Cl                        ##STR24##    188-90    199.        CF.sub.3, H               F  Cl   CO.sub.2 CH.sub.2 CCI                                     55-60    201.        CH.sub.3, H               F  Cl   CO.sub.2 CH(CH.sub.3).sub.2                                     101-103    202.        CF.sub.3, H               F  Cl   SO.sub.2 CH.sub.2 CH(CH.sub.3).sub.2                                     48-51    203.        CF.sub.3, H               F  Cl   SCH.sub.2 CH(CH.sub.3).sub.2                                     71-74    205.        CF.sub.3, H               F  Cl                        ##STR25##    137.5-140    206.        CF.sub.3, H               F  Br   CO.sub.2 CH(CH.sub.3).sub.2                                     98-99    207.        CF.sub.3, H               H  Cl   CO.sub.2 CH(CH.sub.3).sub.2                                     113-115    209.        CF.sub.3, H               F  F    F             97-99    212.        CF.sub.3, H               F  F    OCH.sub.2 CCH 67-68    213.        CF.sub.3, H               F  Cl   CO.sub.2.sup.- K.sup.+                                     133-143    214.        CF.sub.3, H               H  CH.sub.3                       Cl            148-149.5    215.        CF.sub.3, H               F  Cl                        ##STR26##    175-178    216.        CF.sub.3, H               F  Cl                        ##STR27##    125-128    218.        CF.sub.3, H               F  Cl   CO.sub.2 NCHCH(CH.sub.3).sub.2                                     110-117    219.        CF.sub.3, H               F  Cl                        ##STR28##    105-107    220.        CF.sub.3, H               F  Cl                        ##STR29##    oil    221.        CF.sub.3, H               F  Cl   CO.sub.2 NC(CH.sub.3)OCH.sub.2 CH.sub.3                                     oil    222.        CF.sub.3, H               F  Cl   NO.sub.2      164-167    223.        CF.sub.3, H               F  F    CO.sub.2 CH(CH.sub.3 ).sub.2                                     127-129    224.        CF.sub.3, H               F  Br   OCH.sub.2 CCH 105-107.5    225.        CF.sub.3, H               F  Cl   N(COCH.sub.3).sub.2                                     164-169    227.        CF.sub.3, H               F  Cl                        ##STR30##    165-173    228.        CF.sub.3, H               F  CF.sub.3                       CO.sub.2 CH(CH.sub.3).sub.2                                     89-92    229.        CF.sub.3, H               F  OCH.sub.3                       OCH.sub.3     55-60    231.        CF.sub.3, H               F  Cl                        ##STR31##    152-153    232.        CF.sub.3, H               F  Cl                        ##STR32##    84-86    234.        CF.sub.3, H               F  Cl                        ##STR33##    144-147    236.        CF.sub.3, H               F  Cl   OSO.sub.2 CH.sub.3                                     96-99    237.        CHF.sub.2, H               F  Cl   CO.sub.2 CH(CH.sub.3).sub.2                                     oil    240.        CF.sub.3, H               F  Cl   OCH(CH.sub.3)CHCH.sub.2                                     oil    241.        CF.sub.3, H               F  Cl   OCH.sub.2 C(Cl)CH.sub.2                                     103-106    242.        CF.sub.3, H               F  Cl   CO.sub.2 CH(CH.sub.3)CHCH.sub.2                                     79-81    243.        CF.sub.2 H, H               F  Cl   OCH.sub.2 CCH 110-111.5    244.        CF.sub.3, H               F  Cl   OCH.sub.2 CHC(Cl).sub.2                                     106-108    245.        CF.sub.3, H               F  Cl                        ##STR34##    121-123.3    246.        CF.sub.3, H               F  Cl   S(O)CH.sub.2 CH(CH.sub.3).sub.2                                     133-134    247.        CH.sub.2 F, H               F  Cl   CO.sub.2 CH(CH.sub.3).sub.2    248.        CH.sub.2 F, H               F  Cl   OCH.sub.2 CCH    264.        CF.sub.3, H               F  Cl   NCH.sub.2 CH.sub.2 CH.sub.3    265.        CF.sub.3, H               F  OCH.sub.3                       NCH.sub.2 CH.sub.2 CH.sub.3    266.        CF.sub.3, H               F  Cl   NCH.sub.2 CCH    267.        CF.sub.3, H               F  Cl   NCH.sub.2 CHCH.sub.2    268.        CF.sub.3, H               F  Cl                        ##STR35##    269.        CF.sub.3, H               F  Cl   C(OCH.sub.3)NOCH.sub.3    271.        CF.sub.3, H               F  OCH.sub.3                       CO.sub.2 CH(CH.sub.3).sub.2    272.        CF.sub.3, H               F  OCHF.sub.2                       CO.sub.2 CH(CH.sub.3).sub.2    273.        CF.sub.3, H               F  OCF.sub.3                       CO.sub.2 CH(CH.sub.3).sub.2    __________________________________________________________________________     **"subl" means sublimes.

                                      TABLE II    __________________________________________________________________________     ##STR36##    No.       R, R.sup.1            X Y  Z         A   A.sup.1                                   Q  T D  m.p. (°C.)    __________________________________________________________________________       CF.sub.3, H            F Cl OCH(CH.sub.3).sub.2                           CH.sub.2                               CO  -- H CH 98-102       CF.sub.3, H            F Cl OCH.sub.2 CCH                           CH.sub.2                               CH.sub.2                                   -- H CH oil       CF.sub.3, H            F F  H         CO  CO  -- F CH 94-97       CF.sub.3, H            H Cl H         CO  CO  -- H N  119-121       CF.sub.3, H            F Cl H         CO  CO  CH.sub.2                                      H CH 113-115       CF.sub.3, H            H Cl H         CO  CO  CH.sub.2                                      H CH 114-119       CH.sub.3, H            H Cl H         CO  CO  -- H N  154       CH.sub.3, H            H F  H         CS  CO  -- H CH 84.5-87.5       CH.sub.3, H            H F  CN        CO  CO  -- F CH 92-94       CF.sub.3, H            H Cl H         CO  CO  O  H CH 148-152       CF.sub.3, H            H NO.sub.2                 CO.sub.2 CH.sub.3                           CO  CO  O  H CH 152-155    132.       CF.sub.3, H            F Cl H         CO  CO  -- F CH 134-135    __________________________________________________________________________

                                      TABLE III    __________________________________________________________________________     ##STR37##    No. X  L  M   R   R.sup.3                           R.sup.4   m.p. (°C.)    __________________________________________________________________________     84.        H  O  CO  CF.sub.3                      CH.sub.3                           CH.sub.2 CCH                                     100-102     85.        H  O  CO  CF.sub.3                      H    CH.sub.2 CCH                                     203-204.5     88.        F  O  CO  CF.sub.3                      CH.sub.3                           CH.sub.2 CCH                                     147-148     89.        F  O  CO  CF.sub.3                      H    CH.sub.2 CCH                                     182-183     96.        F  O  CO  CF.sub.3                      H    CH.sub.2 CN                                     126-128     97.        F  O  CO  CF.sub.3                      H    CH.sub.2 CHCH.sub.2                                     126-128     98.        F  O  CO  CF.sub.3                      H    CH.sub.2 OCH.sub.2 CH.sub.3                                     151-152    105.        H  O  CO  CF.sub.3                      H    CH.sub.2 CH.sub.2 CH.sub.3                                     170-171    121.        F  O  CO  CF.sub.3                      H    CH.sub.2 SCH.sub.3                                     oil    122.        F  O  CO  CF.sub.3                      H    CH.sub.2 CH.sub.2 CH.sub.3                                     oil    124.        H  S  CO  CF.sub.3                      H    CH.sub.2 CCH                                     165-168    126.        F  O  CO  CF.sub.3                      H    CH.sub.2 C.sub.6 H.sub.5                                     212-216    128.        F  O  CO  CF.sub.3                      H    CH.sub.2 CH(CH.sub.3).sub.2                                     180-181    129.        F  O  CO  CF.sub.3                      H    CH(CH.sub.3)CH.sub.2 CH.sub.3                                     108-109    131.        F  O  CO  CF.sub.3                      H    CH.sub.3  170-173    134.        F  O  CO  CF.sub.3                      H    CH.sub.2 (CH.sub.2).sub.6 CH.sub.3                                     91-94    136.        H  O  CH2 CF.sub.3                      H    CH.sub.2 CH.sub. 2 CH.sub.3                                     68-71    137.        F  O  CO  CF.sub.3                      H    CH.sub.2 CO.sub.2 CH(CH.sub.3).sub.2                                     164-166    138.        F  O  CO  CF.sub.3                      H    H         oil    139.        F  O  CO  CF.sub.3                      H    COCH.sub.3                                     oil    142.        F  O  CO  CF.sub.3                      H    CO.sub.2 CH.sub.3                                     oil    143.        F  O  CO  CF.sub.3                      H    CH(CH.sub.3).sub.2                                     oil    145.        F  O  CO  CH.sub.3                      H    CH.sub.2 CCH                                     192-194    146.        F  O  CO  CF.sub.3                      H    CH(CH.sub.2 CH.sub.3).sub.2                                     oil    147.        H  O  CO  CF.sub.3                      H    CH(CH.sub.3)CCH                                     68-70    149.        F  O  CO  CF.sub.3                      H    CH(CH.sub.3)CN                                     oil    151.        H  O  CO  CF.sub.3                      H    CH.sub.2 OCH.sub.3                                     138-140    154.        H  O  CO  CF.sub.3                      H    CH.sub.2 CHCH.sub.2                                     144-146    155.        F  O  CO  CF.sub.3                      H    CH.sub.2 C(CH.sub.3)CH.sub.2                                     200-202    157.        H  O  CO  CF.sub.3                      H    CH(CH.sub. 3)CH.sub.2 CH.sub.3                                     115-118    165.        F  O  CO  CF.sub.3                      H    CH.sub.2 CH.sub.3                                     148-150    166.        F  O  CO  CF.sub.3                      H    CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3                                     165-167    167.        H  O  CO  CF.sub.3                      H    CH.sub.2 CH.sub.2 OCH.sub.3                                     143-146    171.        H  O  CO  CH.sub.3                      H    CH.sub.2 CCH                                     200-204    179.        F  O  CO  CF.sub.3                      H    CH.sub.2 CH.sub.2 CH.sub.2 Cl                                     138-140    182.        F  O  CO  CF.sub.3                      H                            ##STR38##                                     146-148    184.        F  S  CO  CF.sub.3                      H    CH.sub.2 CHCH.sub.2                                     148-150    188.        F  O  CO  CF.sub.3                      H    CH.sub.2 OCH.sub.3                                     175-176    189.        F  O  CO  CF.sub.3                      H                            ##STR39##                                     oil    200.        F  O  CO  CF.sub.3                      H    CH.sub.2 CON(CH.sub.3).sub.2                                     >200    204.        F  O  CO  CF.sub.3                      H                            ##STR40##                                     180-181    208.        F  O  C O CF.sub.3                      H                            ##STR41##                                     foam    210.        F  O  CO  CF.sub.3                      H                            ##STR42##                                     foam    211.        H  O  CO  CF.sub.3                      H    CH(CH.sub.3).sub.2                                     153-155    217.        H  O  CO  CF.sub.3                      H    CH.sub.2 CH.sub.2 Cl                                     109-110    226.        F  O  CO  CF.sub.3                      H    CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2                                     122-124    230.        F  O  CO  CF.sub.3                      H    CH.sub.2 C(Cl)CH.sub.2                                     178-180    233.        F  O  CO  CF.sub.3                      H    CH.sub.2 CHCCl.sub.2                                     173-175    235.        F  O  CO  CF.sub.3                      CH.sub.2 CH.sub.3                           CH.sub.2 CCH                                     foam    238.        F  O  CO  CF.sub.2 H                      H    CH.sub.2 CCH                                     >200    239.        F  O  CO  CF.sub.3                      H                            ##STR43##                                     foam    249.        F  O  CO  CFH.sub.2                      H    CH.sub. 2 CCH    250.        H  O  CO  CFH.sub.2                      H    CH.sub.2 CCH    251.        H  O  CO  CF.sub.2 H                      H    CH.sub.2 CCH    252.        F  O  CO  CF.sub.2 H                      H    CH.sub.2 CHCH.sub.2    253.        F  O  CO  CF.sub.2 H                      H    CH(CH.sub.3).sub.2    254.        F  O  CO  CF.sub.2 H                      H    CH.sub.2 CH(CH.sub.3).sub.2    255.        F  O  CO  CF.sub.2 H                      H    CH.sub.2 OCH.sub.3    256.        F  O  CO  CFH.sub.2                      H    CH.sub.2 OCH.sub.3    257.        F  O  CO  CFH.sub.2                      H    CH(CH.sub.3).sub.2    258.        F  O  CO  CFH.sub.2                      H    CH.sub.2 CH(CH.sub.3).sub.2    259.        F  O  CO  CFH.sub.2                      H    CH.sub.2 CHCH.sub.2    260.        F  O  CO  CF.sub.3                      H    CH.sub.2 C(O)CH.sub.3    261.        F  O  CO  CF.sub.3                      H    CH.sub.2 CH(OH)CH.sub.3    __________________________________________________________________________

                  TABLE IV    ______________________________________    No.                            m.p. (°C.)    ______________________________________     86.          ##STR44##                178-179     87.          ##STR45##                197.5-199     90.          ##STR46##                152-155     91.          ##STR47##                132-137    119.          ##STR48##                165    120.          ##STR49##                177-178    123.          ##STR50##                195    125.          ##STR51##                185-186    153.          ##STR52##                222-223    170.          ##STR53##                 95.5-98    181.          ##STR54##                148-152    198.          ##STR55##                158-160    262.          ##STR56##    263.          ##STR57##    270.          ##STR58##    275.          ##STR59##                285-287    ______________________________________

                  TABLE V    ______________________________________    NMR DATA    Ex.             (200 MHz, delta scale in ppm,    No.  Solvent    Tetramethylsilane (TMS) standard)    ______________________________________     6.  CDCl.sub.3 1.0(t, 3H), 1.3(d, 3H), 1.6-1.9(m, 2H),                    2.8-3.2(m, 5H), 4.1-4.3(m, 1H),                    6.7(dd, 1H), 7.3(dd, 1H)     12. CDCl.sub.3 3.0(m, 4H), 3.5(s, 3H), 3.5(m, 1H),                    5.2(s, 2H), 7.0(d, 1H), 7.3(d, 1H)     15. CDCl.sub.3 1.8(m, 4H), 2.2(m, 1H), 2.6(m, 1H),                    2.7(t, 2H), 3.5(d, 2H), 4.7(s, 2H),                    6.7(d, 1H), 7.1(d, 1H)     25. CDCl.sub.3 2.6(t, 1H), 2.9-3.3(m, 5H), 4.9(d, 2H),                    6.9(m, 1H), 7.6(m, 1H)     41. d.sub.6 -acetone                    1.3(d, 6H), 3.1(m, 4H), 3.4(m, 1H),                    4.0(m, 1H), 7.4(t, 1H), 7.5(d, 1H)     48. d.sub.6 -acetone                    1.0(d, 6H), 1.4(d, 6H), 1.7(m, 1H),                    2.5-3.0(m, 4H), 4.1(m, 1H), 4.6(m, 1H),                    7.1(m, 1H), 7.4(m, 1H)     50. d.sub.6 -acetone                    1.2(d, 6H), 3.1(m, 4H), 3.5(m, 1H),                    3.8(d, 2H), 4.9(m, 1H), 7.4(dd, 1H),                    7.5(d, 1H)     56. d.sub.6 -acetone                    3.2(m, 4H), 3.7(s, 3H), 3.6(m, 1H),                    3.8(d, 2H), 7.5(dd, 1H), 7.6(d, 1H)     59. d.sub.6 -acetone                    2.5(s, 3H), 3.2(m, 4H), 3.6(m, 1H),                    7.5(t, 1H), 7.6(d, 1H)     80. CDCl.sub.3 1.33(d, 6H), 2.80-3.23(m, 5H),                    5.25(heptet, 1H), 7.65(m, 2H)     83. CDCl.sub.3 2.5(s, 1H), 2.8-3.2(m, 5H), 4.25(d, 2H),                    4.65(s, 2H), 7.2-7.4(m, 2H)    101. d.sub.6 -DMSO                    1.3(t, 6H), 2.9-3.2(m, 4H), 3.6(m, 1H), 4.1                    (quintet, 4H), 4.7(d, 2H), 7.8-8.0(m, 2H)    107. CDCl.sub.3 1.2-1.3(t, 3H), 2.5(q, 2H), 2.9-3.3(m, 5H),                    3.8(s, 2H), 7.25(d, 1H), 7.30(d, 1H)    109. CDCl.sub.3 2.8-3.2(m, 5H), 4.1(s, 2H), 6.9-7.1(q, 1H),                    7.2-7.4(m, 6H)    112. CDCl.sub.3 2.02(s, 1H), 2.64(td, 2H), 2.82-3.28(m, 5H),                    4.39(t, 2H), 7.36(d, 1H), 7.80(dd, 1H)    113. d.sub.6 -DMSO                    1.70(d, 3H), 2.96-3.19(m, 5H), 5.78(m, 1H),                    7.86-8.08(m, 2H)    115. CDCl.sub.3 1.3(t, 3H), 1.4-1.5(d, 3H), 2.8-3.2(m, 5H),                    4.1-4.2(q, 1H), 4.2-4.3(q, 2H), 4.55(d, 1H),                    4.75(d, 1H), 7.2-7.3(d, 1H), 7.3-7.4(d, 1H)    116. CDCl.sub.3 2.8-3.2(m, 5H), 3.37(s, 3H), 3.72(m, 2H),                    4.45(t, 2H), 7.35(d, 1H), 7.78(d, 1H)    117. CDCl.sub.3 1.35(d, 3H), 2.86-3.22(m, 5H), 3.38(s, 3H),                    3.55(m, 2H), 5.35(m, 1H), 7.35(d, 1H),                    7.73(d, 1H)    118. CDCl.sub.3 0.92(t, 3H), 1.35(d, 3H), 1.70(heptet, 2H),                    2.85-3.25(m, 5H), 5.10(sextet, 1H),                    735(d, 1H), 7.7(dd, 1H)    121. d.sub.6 -acetone                    2.2(s, 3H), 3.1(m, 4H), 3.5(m, 1H),                    4.8(s, 2H), 5.1(d, 2H), 6.9(d, 1H), 7.1(t, 1H)    122. d.sub.6 -acetone                    0.9(t, 3H), 1.7(m, 2H), 3.1(m, 4H),                    3.5(m, 1H) 3.9(m, 2H), 4.7(s, 2H),                    7.0(d, 1H), 7.1(d, 1H)    135. CDCl.sub.3 1.65-2.00(m, 2H), 2.20(m, 2H),                    2.45(m, 2H), 2.85-3.25(m, 5H),                    5.20(quintet, 1H), 7.30(d, 1H), 7.75(d, 1H)    138. d.sub.6 -acetone                    3.1(m, 4H), 3.5(m, 1H), 4.7(s, 2H),                    6.8(d, 1H), 6.9(d, 1H), 9.8(bs*, 1H)    139. d.sub.6 -acetone                    2.6(s, 3H), 3.2(bm**, 4H), 3.6(m, 1H),                    4.9(s, 2H), 7.1(d, 1H), 7.7(d, 1H)    142. d.sub.6 -acetone                    3.1(bm, 4H), 3.6(m, 1H), 4.0(s, 3H),                    4.8(s, 2H), 7.0(d, 1H), 7.4(d, 1H)    143. d.sub.6 -acetone                    1.5(d, 6H), 3.1(m, 4H), 3.5(m, 1H),                    4.6(s, 2H), 4.7(m, 1H), 6.9(d, 1H),                    7.2(d, 1H)    144. CDCl.sub.3 1.55(d, 3H), 2.5(d, 1H), 2.8-3.3(m, 5H),                    4.3(m, 1H), 4.55(d, 1H), 4.80(d, 1H),                    7.2(d, 1H), 7.35(d, 1H)    146. d.sub. 6 -acetone                    0.9(d, 6H), 1.8(m, 4H), 3.0(m, 4H),                    3.5(m, 1H), 4.5(bm, 1H), 4.7(s, 2H),                    6.9(d, 1H), 7.2(d, 1H)    149. d.sub.6 -DMSO                    0.9(d, 3H), 3.2(m, 4H), 3.6(m, 1H),                    4.8(s, 2H), 6.0(quintet, 1H), 7.1(d, 1H),                    7.3(d, 1H)    150. CDCl.sub.3 2.75-3.25(m, 5H), 4.6(d, 2H), 5.3(t, 2H),                    6.0-6.1(m, 1H), 7.2(t, 1H), 7.7(dd, 1H),                    8.4(s, 1H)    189. d.sub.6 -acetone                    2.1(m, 4H), 2.3(m, 4H), 3.2(m, 4H),                    3.5(m, 1H), 4.6(s, 2H), 4.7(m, 1H),                    7.0(d, 1H), 7.4(d, 1H)    208. d.sub.6 -acetone                    1.8(m, 1H), 1.9(m, 3H), 3.1(m, 4H),                    3.5(m, 1H), 3.8(m, 2H), 4.2(m, 3H),                    4.7(s, 2H), 6.9(d, 1H), 7.2(d, 1H)    210. d.sub.6 -acetone                    2.2(m, 2H), 3.1(m, 4H), 3.5(m, 1H),                    3.8(m, 2H), 3.9(m, 2H), 4.6(s, 2H),                    5.5(m, 1H), 7.0(d, 1H), 7.3(dd, 1H)    220. d.sub.6 -acetone                    3.0-3.4(m, 4H), 3.55(m, 1H), 5.45(s, 2H),                    7.35(dd, 1H), 7.53(d, 1H), 7.62(d, 1H),                    7.85(td, 1H), 7.98(dd, 1H), 8.59(d, 1H)    221. d.sub.6 -acetone                    1.34(t, 3H), 2.13(s, 3H), 3.0-3.3(m, 4H),                    3.55(m, 1H), 4.22(q, 2H), 7.65(d, 1H),                    7.90(dd, 1H)    235. d.sub.6 -acetone                    1.1(t, 3H), 1.9(m, 2H), 2.8(d, 1H),                    3.1(m, 4H), 3.5(m, 1H), 4.7(m, 3H),                    7.0(m, 2H)    237. d.sub.6 -acetone                    1.5(d, 6H), 2.9-3.2(m, 5H), 5.2(heptet, 1H),                    6.2(tdd, 1H), 7.5(dd, 1H), 7.8(dd, 1H)    239. d.sub.6 -acetone                    2.6(m, 1H), 2.7(m, 1H), 3.1(m, 4H),                    3.5(m, b, 2H), 3.8(dt, 1H), 4.3(dt, 1H),                    4.8(s, 2H), 6.9(d, 1H), 7.2(t, 1H)    240. CDCl.sub.3 1.5(d, 3H), 3.0(m, 5H), 4.65(t, 1H),                    5.15(d, 1H), 5.25(d, 1H), 5.85(m, 1H),                    6.65(dd, 1H), 7.25(d, 1H)    ______________________________________     *bs = broad singlet     **bm = broad multiplet

EXAMPLE A: Preparation of 4-chloro-2-fluoro-5-propargyloxyaniline.

Into a 300 milliliter (ml), three-necked round-bottomed flask equippedwith an overhead stirrer, dropping funnel and thermometer were placed5-acetamido-2-chloro-4-fluorophenol (21.0 gram (g), 0.103 mole) anddimethyl sulfoxide (DMSO) (100 ml). The mixture was stirred at roomtemperature and aqueous potassium hydroxide (KOH) (7.0 g KOH, 88% w/w,1.01 equivalents (eq) dissolved in 10 ml H₂ O) was added dropwise over10 minutes. An exotherm was noted (25° to 40° C.) during the addition.The solution was stirred for 1 hour, and then a solution of propargylbromide (80% in toluene, 12.7 ml, 1.10 eq) was added dropwise. Anexotherm from 25° to 40° C. was noted during addition. The mixture wasstirred at ambient temperature overnight.

In the morning, thin layer chromatography (TLC) (silica gel, 1:1 v/vhexanes/ethyl acetate (EtOAc)) showed that the reaction was complete.The mixture was poured into ice water (600 ml), filtered, washed withwater and dried in vacuo at 50° C. overnight to give the expectedpropargyloxyacetanilide as a tan powder (24.0 g, 96 %, m.p. 142°-5° C.).

Into a 250 ml, three-necked round-bottomed flask equipped with anoverhead stirrer, thermometer and condenser were placed thepropargyloxyacetanilide (9.64 g, 40 mmol), ethanol (absolute, 43 ml),water (56 ml) and concentrated aqueous hydrochloric acid (HCl) (35% w/w,37.5 ml). A heating mantle was used to heat the mixture to reflux withstirring. After 1 hour at reflux (92° C.), TLC (silica gel, 3:1hexanes/EtOAc, v/v) of a basified aliquot indicated that the reactionwas complete. The mixture was poured into ice water (200 ml) and broughtto pH 10 using 50% aq. sodium hydroxide (NaOH) (25 ml) during which timea brown solid precipitated. The mixture was extracted with ether (3×100ml) and the combined organic layers were washed (2×50 ml water, 1×50 mlbrine), and dried over anhydrous magnesium sulfate (MgSO₄). The mixturewas filtered, the solvent evaporated in vacuo and dried overnight at 25°C. to give the expected aniline as a brown oil.

EXAMPLE B: 3-(trifluoromethyl)glutaric anhydride

To 115 mg (5 mmol) of sodium metal (cut into small pieces and washedwith hexanes) in 5 ml of THF was added a solution of diethyl malonate(800 mg, 5 mmol) in 10 ml THF. The mixture was stirred at roomtemperature until all of the sodium metal was consumed (2-3 hours). Acatalytic amount of tetrabutylammonium bromide was added, followed by aTHF solution (10 ml) of ethyl 4,4,4-trifluoro-crotonate (0.84 g, 5mmol). This mixture was warmed to 40° C. and stirred for 17 hours. Aftercooling to 10° C., glacial acetic acid (300 mg, 5 mmol) was added andthe THF was removed in vacuo. The resulting residue was treated with asolution of 87.3% KOH (1.28 g, 20 mmol) in 10 ml water and refluxed for4.5 hours. After cooling to 10° C., 2.5 ml (26 mmol) of conc. HCl wasadded dropwise via pipette and the mixture was again heated to refluxuntil CO₂ evolution had ceased (ca. 1 hour). The solution was cooled to15° C. and extracted with Et₂ O (3×10 ml). The combined organic phaseswere dried over Na₂ SO.sub. 4, filtered and concentrated in vacuo toafford 3-(trifluoromethyl)glutaric acid as a white solid in 95% yield(m.p. 100°-100.5° C.).

Into a 2 liter 3-necked flask equipped with a mechanical stirrer andreflux condenser were added 320 g (1.6 mol) 3-(trifluoromethyl)glutaricacid and 775 ml acetic anhydride. The solution was refluxed for 2.5hours and allowed to cool to room temperature. The majority of theacetic anhydride was removed in vacuo (80° C.) to afford a brown solidwhich was dissolved in 800 ml of CHCl₃ on a steam bath. Following theaddition of 200 ml hexanes, a white precipitate began to form. Furthercrystallization was induced by storage in a refrigerator. The whiteflocculent solid was filtered and oven dried (50° C., 30 mm Hg) toafford 261 g (89% yield) of the desired product, m.p. 88°-91° C.

EXAMPLE 1:N-(4-chloro-2'-fluoro-5'-propargyloxyphenyl)-3-(trifluoromethyl)glutaramicacid

Into a 1 liter three-necked round-bottomed flask equipped with overheadstirrer, dropping funnel, thermometer and nitrogen (N₂) inlet wereplaced 3-(trifluoromethyl)glutaric anhydride (18.2 g, 0.100 mol) andmethylene chloride (CH₂ Cl₂) (250 ml). The mixture was stirred tohomogeneity and a solution of 4-chloro-2-fluoro-5-propargyloxyaniline(19.9 g, 0.100 mol) in CH₂ Cl₂ (50 ml) was added dropwise over 10minutes to give a clear solution. The mixture was stirred overnight atambient temperature, during which time a thick white precipitate wasformed.

In the morning, the reaction mixture was vacuum filtered and washedsparingly with CH₂ Cl₂ to provide the glutaramic acid as a white solid,36.6 g (96% yield), m.p. 140°-2° C.

EXAMPLE 2:N-(4'-chloro-2'-fluoro-5'-propargyloxyphenyl)-3-(trifluoromethyl)glutarimide(Compound 10)

Into a 500 ml, three-necked round-bottomed flask equipped with amagnetic stir bar, condenser, thermometer and nitrogen inlet adapterwere placedN-(4'-chloro-2'-fluoro-5'-propargyloxyphenyl)-3-(trifluoromethyl)glutaramicacid (13.1 g, 0.034 mol), acetic anhydride (150 ml) and sodium acetate(0.45 g). The mixture was stirred and heated to 95° C. overnight.Volatile components were removed by distillation using a shortpathstillhead at a head temperature less than 50° C. (1-5 mm Hg). Theresidue was dissolved in EtOAc (150 ml) and washed (1×100 ml saturatedaqueous sodium bicarbonate (NaHCO₃), 1×100 ml water, 1×100 ml brine),dried (MgSO₄), filtered and evaporated in vacuo to a brown oil. Dryingin vacuo at 50° C. provided a light brown solid (9.8 g, 79% yield, m.p.80°-82° C.). Recrystallization from methanol/water yielded theglutarimide as a tan solid, m.p. 88°-91° C.

Using the same procedures as described in Example 1 and Example 2,Compounds 1-9, 11, 16-18, 20, 21, 23-28, 33, 39-41, 50, 51, 56, 57,59-62, 64, 65, 71, 72, 79-83, 86, 92, 94, 95, 99, 106-109, 115, 119,120, 125, 132, 144, 152, 160, 180, 185, 191,192, 203, 206, 207, 209,212, 214, 223, 224, 228, 229, 241 and 275 as defined in Tables I, II andIV were prepared except the anilino or amino compound (Formula II) was:4-chloro-2-fluoro-5-methoxyaniline, 4-chloro-2-fluoro-5-ethoxyaniline,5-chloro-2-fluoro-5-n-propyloxyaniline,4-chloro-2-fluoro-5-n-butyloxyaniline,4-chloro-2-fluoro-5-isopropyloxyaniline,4-chloro-2-fluoro-5-s-butyloxyaniline,4-chloro-2-fluoro-5-isobutyloxyaniline,4-chloro-2-fluoro-5-hydroxyaniline, 4-chloro-2-fluoro-5-allyloxyaniline,4-chloro-2-fluoro-5-cyanomethoxyaniline, 2,4,6-trifluoroaniline,4-bromo-2-fluoroaniline, 2,4-difluoroaniline, 3,4-dichloroaniline,4-bromo-3-(trifluoromethyl)aniline, p-toluidine,4-chloro-3-propargyloxyaniline, 2,4-dichloro-5-propargyloxyaniline,5-amino-2 -chloropyridine, 4-chloro-2-fluorobenzylamine,4-chlorobenzylamine, 2-amino-5-chlorobenzonitrile,4-(methylthio)aniline, 4-chloro-2-fluoro-5-(isopropylthio)aniline,4-chloro-2-fluoro-5- (isopropyloxycarbonyl)methylthio!aniline, isopropyl5-amino-2-chloro-4-fluorobenzoate, 4-chloro-2-fluoro-5-(methoxycarbonyl)methylthio!aniline, 4-chloro-2-fluoro-5-(carboxy)methylthio!aniline, 5-amino-2-chloro-4-fluorothiophenol,4-chloro-2-fluoro-5-(methylthio)aniline, methyl5-amino-2-chloro-4-fluorobenzoate, 5-amino-2-chloro-4-fluorobenzoicacid, 4-chlorophenoxyamine, 3-methoxycarbonyl-4-nitrophenoxyamine, ethyl5-amino-2-chloro-4-fluorobenzoate, n-propyl5-amino-2-chloro4-fluorobenzoate,4-chloro-2-fluoro-5-(hydroxymethyl)aniline, isopropyl5-amino-2,4-dichlorobenzoate,4-chloro-2-fluoro-5-(methoxymethyl)aniline,4-chloro-2-fluoro-5-(isopropyloxymethyl)aniline,4-chloro-2-fluoro-5-(propargyloxymethyl)aniline, 6-aminoindazole,5-amino-2-chloro-4-fluorotoluene, 5-amino-2-chloro4-fluorobenzaldehyde,3-(propargyloxy)aniline, 3,4-(methylenedioxy)aniline,1,4-benzodioxan-6-amine, 5-amino-2-methylbenzothiazole,4-chloro-2-fluoro-5-(isopropylthiomethyl)aniline,4-chloro-2-fluoro-5-(ethylthiomethyl)aniline,4-chloro-2-fluoro-5-(phenoxymethyl)-aniline,4-chloro-2-fluoro-5-(phenylthiomethyl)aniline, 4-chloro-2-fluoro-5-(1-ethoxycarbonyl)ethoxymethyl!aniline, 4-chloro- 2-fluoro-5-(3-butynyl-2-oxy)methyl!aniline,4-chloro-2-fluoro-5-(methoxyethoxy)aniline, isopropyl3-amino4-fluorobenzoate, 4-chloro- 2,6-difluoroaniline,4-cyano-2-fluoroaniline, 5-amino- 2-chloro-4-fluoroacetophenone,6-amino-3,4-benzocoumarin, 4-(trifluoromethoxy)aniline, 4-nitroaniline,4-(trifluoromethyl)aniline, 4-chloro-5-cyclopentyloxy-2-fluoroaniline,4-chloro-2-fluoro-5-(isobutylthio)aniline, isopropyl5-amino-2-bromo-4-fluorobenzoate, isopropyl 5-amino-2-chlorobenzoate,2,4,5-trifluoroaniline, 2,4-difluoro-5-propargyloxyaniline,3-chloro-4-methylaniline, isopropyl 5-amino-2,4-difluorobenzoate,4-bromo-2-fluoro-5-propargyloxyaniline, isopropyl5-amino-4-fluoro-2-(trifluoromethyl)benzoate,2-fluoro-4,5-dimethoxyaniline or4-chloro-5-(2-chloroallyloxy)-2-fluoroaniline.

In addition, the procedures of Examples 1 and 2 were used to prepareCompounds 30, 35, 38, 4,349, 91, 201, and 237 as described in Tables I,II and III except the appropriate glutaric anhydride of Formula III,i.e., 3-methylglutaric anhydride, 3-ethylglutaric anhydride,3,3-dimethylglutaric anhydride, 3-(fluoromethyl)glutaric anhydride,3-(difluoromethyl)glutaric anhydride, 3-(pentafluoroethyl)glutaricanhydride, 3-isopropylglutaric anhydride, 3-phenylglutaric anhydride orhomophthalic anhydride, was reacted with an anilino compound (FormulaII): 4-chloro-2-fluoro-5-isopropyloxyaniline,4-chloro-2-fluoro-5-propargyloxyaniline, 4-bromo-2-fluoroaniline,isopropyl 5-amino-2-chloro-4-fluorobenzoate or 5-amino-2-chloropyridine.

EXAMPLE 3:N-(4'-chloro-2'-fluoro-5'-(methoxymethoxy)phenyl)-3-(trifluoromethyl)glutaramide(Compound 12)

a. 4-chloro-2-fluoro-5-(methoxymethoxy)nitrobenzene

To 1.12 g (5.9 mmol) of 2-chloro-4-fluoro-5-nitrophenol in 100 ml of CH₂Cl₂ was added 2 ml of dimethoxymethane followed by 7.48 g (53 mmol) ofphosphorous pentoxide. The reaction was stirred at room temperature for3 hours after which time an additional 100 ml of CH₂ Cl₂ was added. Thereaction was poured onto 200 ml of ice and the resulting layers wereseparated. The aqueous phase was extracted once more with CH₂ Cl₂ (1×100ml) and the combined organic phases were washed with water (2×100 ml),dried over MgSO₄ and concentrated to afford 1.16 g (95% yield) of a paleyellow solid 4-chloro-2-fluoro-5-(methoxymethoxy)nitrobenzene.

The nitrobenzene intermediate was converted to the corresponding anilineusing iron and acetic acid as described in Example 13c. The aniline wasconverted to Compound 12 of Table I using the procedures described inExamples 1 and 2.

EXAMPLE 4:N-(4'-chloro-2'-fluoro-5'-(benzenesulphonyloxy)phenyl)-3-(trifluoromethyl)glutarimide(Compound 13)

To a solution ofN-(4'-chloro-2'-fluoro-5'-hydroxyphenyl)-3-(trifluoromethyl)glutarimide(1.64 g, 5.05 retool, Compound 19) in about 20 ml of methylene chloridewas added via syringe nearly 2.5 eq. of pyridine (1 ml) which had beenfreshly distilled from CaH₂. Then a solution of benzenesulfonyl chloride(0.64 ml, 5.0 mmol) in 4.5 ml of methylene chloride was slowly addeddropwise to the reaction mixture with ice bath cooling. The reactionmixture was allowed to warm to room temperature and stirred for 12hours. Then there was added 0.17 g of additional glutarimide and thereaction mixture was stirred at room temperature for an additional 12hours. The reaction mixture was poured into 50 ml of water and thelayers were separated. The organic layer was evaporated in vacuo and theresidue was dried in the vacuum oven (20-50 Torr, 50° C.). The resultingbrown solid was rinsed with approximately 5 ml of methylene chloride andsuction filtered to yield 1.9 g (82% yield) of the desired product as anoff-white powder (m.p. 214°-215° C.).

Using substantially the procedure described in this example, Compound190 was prepared except ethanesulfonyl chloride was used in place ofbenzenesulfonyl chloride.

EXAMPLE 5:N-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-4-(trifluoromethyl)-2-piperidone(Compound 14)

a.N-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-5-hydroxy-3-(trifluoromethyl)pentanamide

To a solution ofN-(4'-chloro-2'-fluoro-5'-isopropyloxy-phenyl)-3-(trifluoromethyl)glutaramicacid (4.32 g, 11.4 mmol) in 20 ml of tetrahydrofuran, (freshly distilledfrom sodium/benzophenone) was slowly added 10M borane-methyl sulfidecomplex (1.18 ml) via syringe. The temperature was maintained at 10°-20°C. with an ice bath while vigorous bubbling was evident. The mixture wasallowed to warm slowly to room temperature and stirred 150 hrs whilekept under nitrogen, heated to 55° C. for 6 hours, then cooled to roomtemperature and allowed to stand for 16 hours. The flask was cooled inan ice/water bath, then 7 ml of methanol (MeOH) were added slowly viaaddition funnel. The reaction mixture became too thick to continuestirring. It was allowed to warm slowly to room temperature, when thestir bar was again able to stir the mixture. The MeOH and THF wereremoved in vacuo (20-50 Torr) and the residue was flash chromatographed(2"×7" column, 3:1 hexanes/ethyl acetate, 75 ml fractions). Fractions18-45 were combined and the solvent was removed in vacuo. The residuewas dried in vacuo at 50° C. to yield 1.66 g (39% yield) of thepentanamide as a nearly colorless oil.

b.N-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-5-chloro-3-(trifluoromethyl)pentanamide

To a solution ofN-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-5-hydroxy-3-(trifluoromethyl)pentanamide(1.2 g, 3.2 mmol) in 100 ml methylene chloride, was added thionylchloride (0.24 ml) in one portion via pipette. The solution turnedbrown. It was heated to 40°-50° C. for about 7 hours, kept at roomtemperature for 64 hours, heated to 40° C. for 3 hours, then stirred atroom temperature for 18 hours. Then additional thionyl chloride (0.1 ml)was added and heating to 40° C. was resumed for about 4 hours. Thereaction mixture was cooled to room temperature and the solvent wasremoved in vacuo. The residue was dried in vacuo (50° C.) and theresulting golden brown, semi-solid mixture was purified via flashchromatography (20 ml fractions, 2'×7' column, 1:9 ethylacetate/hexanes) to yield a brown solid, m.p. of 57°-63° C.

c.N-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-4-(trifluoromethyl)-2-piperidone

To a tetrahydrofuran (16 ml) solution of 1.4 g (3.6 mmol) ofN-(4'-chloro-2'-fluoro-5'-isopropyloxyphenyl)-5-chloro-3-(trifluoromethyl)pentanamidewere added 16 ml water and 2 ml 50% NaOH (aq). The mixture was heated to50° C. while stirring vigorously. After 6 hours the reaction was allowedto cool to room temperature, stirring was stopped and the aqueous layerwas removed. The organic layer was evaporated in vacuo, then the residuewas taken up in ether (50 ml), washed with water (2×50 ml) and thenbrine. The original aqueous layer was extracted with a second 50 mlportion of ether, the combined organic layers were washed with brine (50ml) and dried (MgSO₄). The solvent was removed in vacuo to yield 1.3 g.of a brown solid which was recrystallized from hexanes to yield 0.81 g(64% yield) of a brown solid (m.p. 98°-102° C.).

EXAMPLE 6:N-(4'-chloro-2'-fluoro-5'-propargyloxyphenyl)-4-(trifluoromethyl)piperidine(Compound 15)

Into a three-necked round-bottomed flask were placed 0.56 g (15 mmol)lithim aluminum hydride and 60 ml tetrahydrofuran. A thimble containing3.60 g (10.0 mmol) ofN-(4'-chloro-2'-fluoro-5'-propargyloxyphenyl)-3-(trifluoromethyl)glutarimidewas placed in a Soxhlet extractor and attached to the reaction flask.The oil bath was heated to 85° C. and 11 ml THF and 25 ml ether wereadded. After six hours the majority of the glutarimide had beenextracted into the reaction mixture producing a grey solid in thereaction flask which prevented stirring. The reaction mixture wasallowed to cool to room temperature. Water (0.56 ml) was added slowlyfollowed by 15% NaOH (0.56 ml). Then additional water (1.68 ml) wasadded in order to precipitate lithium salts. The mixture was suctionfiltered and the solid was rinsed with ether. The filtrate wasevaporated in vacuo to yield 3.4 g of a brown oil. The oil waschromatographed (silica gel, 3:1 hexanes/methylene chloride) to yield100 mg (3% yield) of the desired product as an oil.

EXAMPLE 7:N-(4'-chloro-2'-fluoro-5'-hydroxyphenyl)-3-(trifluoromethyl)glutarimide(Compound 19)

a.N-(4'-chloro-2'-fluoro-5'-hydroxyphenyl)-3-(trifluoromethyl)glutaramicacid

Into a 1 liter, three-necked round-bottomed flask equipped with amagnetic stir bar, thermometer, dropping funnel, condenser and N₂ inletwere placed 4-chloro-2-fluoro-5-hydroxyaniline (25.7 g, 0.159 mol),water (24 ml), acetic acid (8.4 ml) and tetrahydrofuran (THF) (48 ml).The mixture was stirred to homogeneity, then heated to 40° C. and asolution of 3-(trifluoromethyl)glutaric anhydride (34.8 g, 0.191 mol) inTHF (60 ml) was added dropwise via an addition funnel and an exotherm ofabout 3°-4° C. was noted. The resulting mixture was heated to 50° C. forthree hours then cooled to ambient temperature.

The reaction mixture was poured onto 600 ml of ice. When the ice melted,the solid was isolated via suction filtration through a coarse sinteredglass funnel. The solid was washed well with water and dried in vacuo at50° C. to yield the glutaramic acid as a grey solid (51.91 g, 95% yield,m.p. 171°-174° C.).

b.N-(4'-chloro-2'-fluoro-5'-hydroxyphenyl)-3-(trifluoromethyl)glutarimide

Into a 250 ml three-necked round-bottomed flask equipped with stir bar,N₂ inlet and rubber septa were placedN-(4'-chloro-2'-fluoro-5'-hydroxyphenyl)-3-(trifluoromethyl)glutaramicacid (9.51 g, 24 mmol) and EtOAc (75 ml). The mixture was stirred tohomogeneity and thionyl chloride (99+%, 3.87 ml, 2 eq) was added viasyringe, followed by 0.25 equivalent of anhydrous N,N-dimethylformamide.The reaction was heated to about 80° C. for approximately 6 hours, andthen allowed to stand overnight at room temperature.

The reaction mixture was poured into 125 ml water and was extractedtwice with a total of 100 ml of EtOAc. The organic layers were combined,then washed two times with 100 ml of water and once with 50 ml of brine.The organic layer was separated, dried with MgSO₄, evaporated underreduced pressure, and dried in vacuo (20-50 Torr, 50° C.). The residuesolidified on sitting to yield 8.6 g (99% yield) of the glutarimide as adark brown solid, m.p. 112°-114° C.

Using the same procedure as used in this example, Compound 58 describedin Table I above was also prepared except the anilino compound (FormulaII) was 5-amino-2-chloro-4-fluorothiophenol.

EXAMPLE 8: N-(4'-bromophenyl)-3-(trifluoromethyl)glutarimide (Compound22)

Into a 50 ml 1-necked, round-bottomed flask containing a stir bar wereplaced 2.50 g (7.96 mmol)N-(4'-bromophenyl)-3-(trifluoromethyl)glutaramic acid (prepared asdescribed in Example 1 from the appropriate aniline and glutaricanhydride) and acetyl chloride (15 ml). The mixture was heated to refluxfor 6 hours resulting in a dear, light grey solution. The acetylchloride was removed via atmospheric distillation through a short pathdistillation head. The resulting light grey crystalline solid wastriturated with hexanes, filtered and washed with hexanes to yield anoff-white crystalline solid which was dried in vacuo at 50° C. to yield2.10 g (89% yield) of product, m.p. 163°-4° C.

Using the same procedure as used in this example, Compounds 29, 34, 37,42, 63, 66, 68, 69 and 70 described in Tables I and II were alsoprepared.

EXAMPLE 9: N-(4'-fluorophenyl)-3-methylthioglutarimide (Compound 36)

A mixture of 1.02 g (4.68 mmol) ofN-(4'-fluorophenyl)-3-methylglutarimide (Compound 66), 0.88 g (2.2 mmol)of 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide(known as Lawson's Reagent), and 6 ml of hexamethylphosphoramide in a 50ml round-bottomed flask was warmed to 95°-100° C. for 21 hours. Anadditional 1.05 g (2.5 mmol) of Lawson's Reagent were added and heatingto 100° C. was continued for an additional 30 hours. The mixture wasallowed to cool to room temperature and water (50 ml) was added. Themixture was extracted with ether (4×50 ml). The organic portions werecombined, dried over MgSO₄ and the solvent was removed in vacuo. Theresulting 2 g of orange oil were purified via flash chromatography(silica gel, 1:1 hexanes/methylene chloride) to yield 300 mg (28% yield)of yellow oil which solidified to a solid: m.p. 84.5°-87.5° C.

EXAMPLE 10: N- 4'-chloro-2'-fluoro-5'-(phenylthio)methoxy!-phenyl!-3-(trifluoromethyl)glutarimide (Compound52)

While kept under N₂, 0.15 g (3.7 mmol, 60% dispersion in oil) sodiumhydride was washed with pentanes (2×0.5 ml), then suspended in 2 ml ofdry THF (fleshly distilled from sodium/benzophenone). To the suspension,cooled in an ice bath, were added 1.1 g (3.4 mmol) ofN-(4'-chloro-2'-fluoro-5'-hydroxyphenyl)-3-(trifluoromethyl)glutarimide(Compound 19) dissolved in 3.5 ml of dry THF (freshly distilled fromsodium/benzophenone) and two 1 ml rinses of dry THF. The reaction wasthen allowed to warm to room temperature and stirred for 15 minutes. Theflask was again cooled in an ice bath while a solution of chloromethylphenyl sulfide (0.46 ml, 0.54 g, 3.4 mmol) in 3 ml dry THF was addeddropwise. The reaction mixture was allowed to warm slowly to roomtemperature and stirred for about 24 hours, then warmed to 50° C. for 54hours. The THF was evaporated in vacuo (2-10 Torr) and the reactionmixture was taken up in 12 ml anhydrous dimethylformamide. The reactionwas heated to 100° C. for 8 hours then cooled to room temperature. Thereaction mixture was suction filtered through a short pad of neutralalumina and rinsed with 30 ml EtOAc. The filtrate was evaporated invacuo and the residue was dried in the vacuum oven for 12 hours (20-50Torr, 50° C.). The resulting oil was vacuum distilled (2-10 Torr, 70°C.). The residue was chromatographed (silica gel, 1:1 hexanes/methylenechloride) to yield 350 mg (23% yield) of the desired product as a whitesolid, m.p. 108°-109.5° C.

Using the procedure as used in this example, Compounds 53, 54, 55, 73,and 76 described in Table I were also prepared except the appropriatelysubstituted alkyl halide (e.g., benzyl chloride for Compound 73) wasused in place of the chloromethyl phenyl sulfide.

EXAMPLE 11: N-(4'-chlorophenyl)-3-methylglutarimide (Compound 67)

Combined in a 500 ml one-necked round-bottomed flask containing a stirbar were 3-methylglutaric anhydride (6.41 g, 0.05 mol), p-chloroaniline(6.39 g, 0.05 mol) and tetrahydrofuran (50 ml). The mixture was stirredto homogeneity and had a delayed (about 5 min.) mild exotherm. The paleyellow solution was allowed to stand overnight.

The mixture was evaporated in vacuo, then dried under vacuum of about2-10 Torr with additional heat, to give a tan solid. The solid was driedovernight in a vacuum oven to yieldN-(4'-chlorophenyl)-3-methylglutaramic acid as a tan solid (12.72 g,99.4%, m.p. 116°-118° C.).

The glutaramic acid was treated as described in Example 8 to yieldN-(4'-chlorophenyl)-3-methylglutarimide (96% yield, m.p. 163°-164° C.).

Using the procedure as used in this example, Compounds 31 and 32described in Table I were also prepared.

EXAMPLE 12: N-5'-(2-methylpropyloxycarbonyl)-4'-chloro-2'-fluorophenyl!-3-(trifluoromethyl)glutarimide(Compound 75)

a.N-(5'-chlorocarbonyl-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide

To a mixture ofN-(5'-carboxy-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide(Compound 62) (3.0 g, 8.5 mmol) and 35 ml toluene was added thionylchloride (0.80 ml, 1.3 g, 1.1 mmol) followed by 2 drops ofN,N-dimethylformamide and the suspension was heated to 90° C. for twohours. The resulting clear, orange solution was cooled to roomtemperature and the solvents were removed in vacuo (1 mm Hg). TheresultingN-(5'-chlorocarbonyl-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide,a dark semisolid, could be used without further purification.

b. N-5'-(2-methylpropyloxycarbonyl)-4'-chloro-2'-fluorophenyl!-3-(trifluoromethyl)glutarimide

A mixture ofN-(5'-chlorocarbonyl-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide(3.1 g, 8.3 mmol) and 20 ml THF was cooled to 0°-10° C. and2-methylpropanol (0.80 ml, 0.64 g, 8.6 mmol) was added followed bytriethylamine (1.2 ml, 0.86 g, 8.5 mmol). A white precipitate began toform as the reaction mixture was allowed to warm to room temperature.The suspension was stirred at room temperature overnight, forming athick white slurry. The reaction mixture was partitioned between water(50 ml) and ethyl acetate (50 ml) and the layers were separated. Theaqueous phase was extracted with ethyl acetate (3×25 ml) and thecombined organic layers were washed (1×25 ml sat'd NaHCO₃, 1×25 mlbrine) and dried over MgSO₄. Concentration afforded 3.1 g of anorange-brown solid which was passed through a silica gel column (100 g)with 50% ethyl acetate/hexanes. Recrystallization from methanol/wateryielded 2.8 g (82% yield from the carboxylic acid) of the expectedproduct as a tan solid, m.p. 82°-85° C.

Using the same procedure as used in this example, Compounds 74, 77, 78,100-104, 110-114, 116-118, 127, 130, 133, 135, 161-164, 194, 195, 197,199, 215, 218-221 and 242 described in Table I were also prepared exceptthe appropriately substituted alcohol, thiol, oxime, oximidate, amine oramine hydrochloride (e.g. isopropylamine for Compound 78) was used inplace of the 2-methylpropanol.

EXAMPLE 113:4-propargyl-6-(N-(3-(trifluoromethyl)glutarimido))-2H-1,4-benzoxazin-3(4H)-one(Compound 85)

a. 6-nitro-2H-1,4-benzoxazin-3(4H)-one

To a mixture of 10.6 g (182 mmol) of potassium fluoride and 55 ml ofanhydrous dimethylformamide was added 7.76 ml (72 mmol) of ethylbromoacetate and the reaction mixture was stirred at room temperaturefor 15 minutes. Then 10.79 g (70.0 mmol) of 2-amino-4-nitrophenol wasadded and the reaction mixture was heated to 55° C. for 6 hours. Thereaction mixture was cooled slowly to room temperature, stirred for 12hours and poured onto 300 ml ice. The solid which formed was filteredoff, washed with water and dried (20-50 Torr, 50° C., 16 hrs). Theresulting orange solid was taken up in 100 ml EtOAc and 100 ml H₂ O. Theaqueous layer was extracted with EtOAc (2×100 ml). The organic layerswere then combined and washed with water (3×150 ml) and 10% HCl anddried (MgSO₄). The solvent was removed in vacuo and the resulting solidwas recrystallized from ethylene dichloride to yield 3.6 g (27% yield)of 6-nitro-2H-1,4-benzoxazin-3(4H)-one as an orange solid, m.p.221°-223° C.

b. 6-nitro-4-propargyl-2H-1,4-benzoxazin-3(4H)-one

While kept under N₂, 0.81 g (20 mmol) of sodium hydride (60% dispersionin oil) was washed with 3 ml of pentanes and suspended in 20 ml ofanhydrous dimethylformamide. While cooling with an ice/brine bath, 3.59g (18.5 mmol) of 6-nitro-2H-1,4-benzoxazin-(4H)-one was added through adry powder funnel (exotherm of about 5° C.). An additional 10 ml of DMFwas added and the mixture was stirred at 0° C. for 30 minutes. There wasthen added 2.06 ml (18.5 mmol) of an 80% solution of propargyl bromidein toluene and the mixture was stirred at room temperature for 12 hrs.The reaction mixture was poured into 50 ml of water and extracted withEtOAc (2×50 ml). The organic layers were combined, washed with water(2×50 ml) and dried (MgSO₄). The solvent was removed in vacuo to yield6-nitro4-propargyl-2H-1,4-benzoxazin-3 (4H)-one as a yellow solid, 4 g(93% yield).

c. 6-amino-4-propargyl-2H-1,4-benzoxazin-3(4H)-one

To a slurry of 5.1 g (91 mmol) of iron powder in 42.5 ml of 5% aqueousacetic acid was added dropwise a solution of 4 g (17 mmol) of6-nitro-4-propargyl-2H-1,4-benzoxazin-3(4H)-one dissolved in 42.5 ml ofglacial acetic acid and 42.5 ml of EtOAc. The reaction mixture washeated to gentle reflux for 1 hour then cooled to room temperature. Theiron was removed by suction filtration. EtOAc (50 ml) was added to thefiltrate and the layers were separated. The aqueous phase was extractedwith EtOAc (2×50 ml) and the organic layers were combined, washed withsaturated aqueous sodium bicarbonate solution (100), and dried (MgSO₄).The solvent was removed in vacuo to yield a thin brown oil which wastaken up in 50 ml of water and reextracted with EtOAc (3×50 ml). Theorganic layers were combined, washed with water (2×50 ml) and then dried(MgSO₄). The solvent was removed in. vacuo to yield 2.55 g (75% yield)of 6-amino-4-propargyl-2H-1,4-benzoxazin-3 (4H)-one, a dark brown solid,m.p. 136°-140° C.

The 6-amino-4-propargyl-2H-1,4-benzoxazin-3(4H)-one was reacted with3-(trifluoromethyl)glutaric anhydride as described in Examples 1 and 2to yield the desired product, m.p. 203°-204.5° C.

Using the same procedure as used in this example, Compounds 84, 90 and171 described in Tables III and IV were a/so prepared except methyl2-chloropropionate was used in place of ethyl bromoacetate for Compound84; phosgene in ethyl acetate was used to react with the2-amino-4-nitrophenol for Compound 90; and 3-methylglutaric anhydridewas used in place of 3-(trifluoromethyl)glutaric anhydride for Compound171.

Using the same procedure as used in parts b and c of this example,Compounds 87, 123, 153, and 170 were prepared starting from6-nitroindole, 6-nitroindoline and 6-nitroindazole.

EXAMPLE 14:7-fluoro-2-methyl-4propargyl-6-(N-(3-(trifluoromethyl)-glutaramido))-2H-1,4-benzoxazin-3(4H)-one(Compound 88)

a. 2-(3'-fluorophenoxy)propionic acid

To a solution of m-fluorophenol (24.2 g, 0.22 mol) in 79.2 ml of 25%aqueous sodium hydroxide heated to 45° C. with an oil bath was added29.5 ml (0.26 mol) methyl 2-chloropropionate. The reaction mixture washeated to 80° C. for 17 hours and then allowed to cool. When thetemperature reached about 40° C., concentrated HCl (25 ml) was added andthe reaction mixture was allowed to cool to room temperature. Thereaction mixture was extracted twice with 100 ml ethyl ether. Theorganic layers were combined and washed with 200 ml of 1.5M aqueoussodium carbonate. The aqueous layer was separated and acidified to pH 1,by pH test paper, by adding concentrated HCl. The acidified aqueouslayer was extracted with 200 ml ethyl ether. The organic layer wasseparated, dried with MgSO₄ and filtered. The solvent was removed invacuo to yield 17 g (41% yield) of 2-(3' -fluorophenoxy)propionic acidas a yellow solid (m.p. 72.5°-74° C.).

b. 2-(2',4'-dinitro-5'-fluorophenyl)propionic acid

To a solution of 5 g (25 mmol) of 2-(3'-fluorophenoxy)propionic acid in11.55 ml of concentrated sulfuric acid (H₂ SO₄) was added slowly via anaddition funnel a mixture of 3.59 ml of 70% nitric acid (2.1 eq.) and3.2 ml of concentrated H₂ SO₄ with ice bath cooling. The reactionmixture was then allowed to warm slowly to room temperature and stirredfor 3 hours. The reaction mixture was poured onto 200 ml of ice waterand the resulting solid was collected by filtration and dried (20-50Torr, 50° C.) for 12 hours to yield 3.6 g (50% yield) of2-(2',4'-dinitro-5'-fluorophenyl)propionic acid, m.p. 141°-142° C.

c. 6-amino-7-fluoro-2-methyl-2H-1,4-benzoxazin-3(4H)-one

To a suspension of 5.05 g (90 mmol) of iron powder in 26.5 ml of 5%aqueous acetic acid was added dropwise a solution of 3.6 g (12.5 mmol)of 2-(2',4'-dinitro-5'-fluorophenyl)propionic acid in 26.5 ml of EtOAcand 26.5 ml of glacial acetic acid. The reaction mixture was heated to agentle reflux for 1 hour and then allowed to cool to room temperature.The iron was removed by suction filtration through a small pad ofCelite® and the filter pad was rinsed with 50 ml of EtOAc. The filtratewas transferred to a separatory funnel and the phases were separated.The aqueous layer was extracted with EtOAc (3×50 ml) and the combinedorganic phases were washed with sodium bicarbonate (2×50 ml), dried overMgSO₄ and filtered. The solvent was removed from the filtrate in vacuoto yield 1.5 g (61% yield) of6-amino-7-fluoro-2-methyl-2H-1,4-benzoxazin-3(4 H)-one as a brown solid,m.p. 208°-211 ° C.

d. 6-amino-7-fluoro-2-methyl-4-propargyl-2H-1,4-benzoxazin-3(4H)-one

While kept under N₂, 0.30 g (7.4 mmol) of sodium hydride (60% dispersionin oil) was washed with 1 ml pentanes and then suspended in 2 mlanhydrous dimethylformamide. A solution of 1.36 g (6.9 mmol) of6-amino-7-fluoro-2-methyl-2H-1,4-benzoxazin-3(4H)-one in 10 ml ofdimethylformamide was added to the sodium hydride slurry slowly bysyringe with ice cooling and the reaction mixture was stirred at roomtemperature for 0.5 hr. There was then added 0.77 ml (8.6 mmol) ofpropargyl bromide by syringe with ice bath cooling. The reaction mixturewas allowed to warm to room temperature, stirred for 84 hours and thenpoured into 50 ml of water. The resulting mixture was extracted withEtOAc (2×50 ml) and the organic layers were combined and washed withwater (3×50 ml), dried over MgSO₄ and filtered. The solvent was removedin vacuo to yield a golden solid which was recrystallized fromchloroform to yield 0.66 g of 6-amino-7-fluoro-2-methyl-4-propargyl-2H-1,4-benzoxazin-3(4H)-one as a brown solid, m.p. 142°-145° C.

The 6-amino-7-fluoro-2-methyl-4-propargyl-2H-1,4-benzoxazin-3(4H)-onewas reacted with 3-(trifluoromethyl)glutaric anhydride as described inExamples 1 and 2 to obtain the desired product, m.p. 147°-148° C.

Using the same procedures as used in this example, Compounds 89, 97,137-139, 155, 182, 208, 210, 226, 230 and 233 described in Table IIIwere also prepared except that the procedure of Example 17a was used inplace of part a and the appropriately substituted alkyl halide ormesylate (e.g. allyl bromide for Compound 97) was used in place ofpropargyl bromide.

Using the same procedure as used in this example, Compound 235 wasprepared except the procedure of Example 17a was used in place of part aand ethyl 2-bromobutyrate was used in place of methyl bromoacetate.

This procedure was also used to prepare Compound 145 except that3-methylglutaric anhydride was used in place of3-(trifluoro-methyl)glutaric anhydride.

EXAMPLE 15: N-4'-chloro-2'-fluoro-5'-(O-methyloximyl)phenyl!-3-(trifluoromethyl)glutarimide(Compound 93)

To a suspension of methoxylamine hydrochloride (0.55 g, 6.6 mmol) inabsolute ethanol (10 ml), was added pyridine (0.52 g, 6.6 ml) viapipette. The reaction was stirred for one hour at room temperature thenN-(4'-chloro-2'-fluoro-5'-formylphenyl)-3-(trifluoromethyl)-glutarimide(2.03 g, 6.0 mmol) (Compound 94) was added as a solid. Additionalethanol (31 ml) was added and the resulting amber solution was stirredunder nitrogen overnight. The solvent was removed in vacuo and theresidue was partitioned between ethyl acetate and water. The organicphase was washed with 2.5% HCl (1×25 ml), and brine (1×25 ml), thendried over MgSO₄. Concentration afforded a tan solid, which wasrecrystallized from MeOH/H₂ O to yield the desired glutarimide as tancrystals (1.33 g, 60% yield, m.p. 150.5°-152.5° C.).

Using the same procedure as used in this example, Compounds 150, 156,158, 159, 168, 186, 187 and 205 described in Table I were also preparedusing the appropriate alkoxy amine or alkoxy amine salt in place ofmethoxylamine hydrochloride.

Using the same procedure as used in this example, Compounds 172-176 and178 were prepared exceptN-(4'-chloro-2'-fluoro-5'-acetylphenyl)-3-(trifluoromethyl)glutarimide(Compound 95) was used in place of Compound 94 and was reacted with theappropriate alkoxy amine or alkoxy amine salt.

EXAMPLE 16:4-propargyl-6-(N-(3-(trifluoromethyl)glutarimido))-2H-1,4-benzthiazin-3(4H)-one(Compound 124)

a. ethyl S-(2,4-dinitrophenyl)mercaptoacetate

Into a 100 ml round-bottomed flask were placed 14.8 g (10 ml, 79.6 mmol)2,4-dinitrofluorobenzene, THF (20 ml, freshly distilled from sodiumbenzophenone) and triethylamine (11.1 ml, 79.6 mmol). The reaction wascooled in an ice bath while 9.55 g (8.73 ml, 79.6 mmol) ethyl2-mercaptoacetate dissolved in THF (10 ml) was added dropwise. Theresulting nearly black solution was allowed to warm slowly to roomtemperature and stirred 18 hours. The reaction mixture was poured onto150 ml ice and the resulting layers were separated. The aqueous phasewas extracted with EtOAc (2×125 ml). The organic layers were combinedand washed with water (100 ml), dried over MgSO₄ and concentrated todryness in vacuo to yield 16.9 g of red-brown solid (74.1% yield).

b. 6-amino-2H-1,4-benzthiazin-3(4H)-one

To a suspension of iron powder (15 g, 0.27 mol) in 21.7 mi of 5% aqueousacetic acid was added dropwise via addition funnel, a solution of ethylS-(2,4-dinitrophenyl)mercaptoacetate (5.91 g, 20.6 mmol) in 20.6 mlglacial acetic acid and 21 ml EtOAc. The reaction mixture was heated to80° C. for 2 hours, then cooled to room temperature. The iron wasremoved by suction filtration and the filtrate was extracted with EtOAc(3×75 ml). The combined organic layers were washed once with 100 mlwater and twice with 100 ml saturated aqueous sodium bicarbonate, dried(MgSO₄) and concentrated to dryness in vacuo to yield 2.3 g of a darkbrown solid.

The 6-amino-2H-1,4-benzthiazin-3(4H)-one was alkylated with propargylbromide as described in Example 13b, then converted to Compound 124using the procedures described in Examples 1 and 2.

Compound 184 was prepared using the above procedure except that2,4-dinitro-1,5-difluorobenzene was used in place of2,4-dinitrofluorobenzene.

EXAMPLE 17: 7-fluoro4-isobutyl-6-N-(3-(trifluoromethyl)-glutaramido))-2H-1,4-benzoxazin-3(4H)-one (Compound 128)

a. methyl 5-fluoro-2-nitrophenoxyacetate

To 10 g (63.7 mmol) of 5-fluoro-2-nitrophenol in 100 ml of methyl ethylketone was added 10.5 g (76.4 mmol) of finely ground potassium carbonatefollowed by 10.7 g (70.1 mmol) of methyl bromoacetate. The resultingsuspension was refluxed for 6 hours and then stirred at room temperatureovernight. During this time it went from a deep red color to paleyellow. The reaction was poured into one liter of water, the layers wereseparated and the aqueous layer was extracted twice more with EtOAc(2×100 ml). The organics were combined, dried (Na₂ SO₄), filtered andevaporated to dryness in vacuo to give 13.3 g (91% yield) of methyl5-fluoro-2-nitrophenoxyacetate as a light yellow solid (m.p. 85°-87°C.).

b. 7-fluoro-2H-1,4-benzoxazin-3(4H)-one

To 500 mg of 5% Pd/C in a Parr bottle was added 100 ml of EtOH followedby 5.0 g (21.8 mmol) of methyl 5-fluoro-2-nitrophenoxyacetate. The flaskwas placed in a Parr Apparatus, evacuated and then charged withhydrogen. The suspension was then shaken for 2 hours. After evacuatingthe flask and recharging with nitrogen, the solids were removed byvacuum filtration through Celite®. Since some product does precipitate,the filter cake is repeatedly rinsed with EtOAc (200 ml). The filtrateis refluxed for 4 hours and then evaporated to dryness in vacuo to givethe desired material, 7-fluoro-2H-1,4-benzoxazin-3(4H)-one, as a whitesolid (m.p. 201°-202° C.) in quantitative yield.

c. 7-fluoro-4-isobutyl-2H-1,4-benzoxazin-3(4H)-one

To 3.96 g (99 mmol) of hexanes washed 60% sodium hydride in 150 ml ofN,N-dimethylformamide was added portionwise as a solid 15 g (90 mmol) of7-fluoro-2H-1,4-benzoxazin-3(4H)-one. When the addition was complete thereaction was stirred at room temperature for 10 min, after which time19.8 g (108 mmol) of isobutyl iodide was added. The reaction was thenstirred overnight before quenching into 200 ml of water. The aqueousphase was extracted with EtOAc (2×150 ml) and the combined organics weredried over Na₂ SO₄, filtered and evaporated in vacuo to give the desiredalkylated product, as a yellow oil (13 g, 65% yield).

d. 7-fluoro-4-isobutyl-6-nitro-1,4-benzoxazin-3-(4H)-one

To 2.50 g (11.2 mmol) of 7-fluoro-4-isobutyl-2H-1,4-benzoxazin-3(4H)onein 25 ml of acetic anhydride was added dropwise over 10 min. a solutionof 2.5 g (26.9 mmol) of 70% nitric acid in 5 ml of glacial acetic acid.After the addition was complete, the reaction was stirred for 1 hour atroom temperature then it was quenched by pouring into 50 ml ofice/water. The resulting white precipitate was collected by vacuumfiltration and dried in a vacuum oven at 60° C. overnight to yield 2.71g (90% yield) of the desired nitrated product, m.p. 108°-110° C.

e. 6-amino-7-fluoro-4-isobutyl-1,4-benzoxazin-3(4H)-one

To 2.82 g (50.5 mmol) of iron powder suspended in 30 ml of 5% glacialacetic acid was added dropwise over 0.5 hour a solution of 2.71 g (10.1mmol) of 7-fluoro-4-isobutyl-nitro-1,4-benzoxazin-3(4H)one in 60 ml of1:1 EtOAc/glacial acetic acid. After addition was complete, the reactionwas refluxed for 2 hours then the solids were removed by vacuumfiltration. The filtrate was extracted with EtOAc (2×100 ml) and thecombined organic layers were washed with NaHCO₃ (sat'd, 2×150 ml) anddried over Na₂ SO₄ before filtering and concentrating (in vacuo) to give2.32 g (96% yield) of the desired aniline,6-amino-7-fluoro-4-isobutyl-1,4-benzoxazin-3(4H)-one, as a redsemisolid.

The 6-amino-7-fluoro-4-isobutyl-1,4-benzoxazin-3(4H)-one was reactedwith 3-(trifluoromethyl)glutaric anhydride as described in Examples 1and 2 to yield the desired product, m.p. 180°-181° C.

Using the appropriate alkylating agent in place of isobutyl iodide instep c, the above procedures were used to prepare Compounds 96, 98, 122,126, 129, 131,134, 143, 146, 149, 165, 166, 189 and 204. Compound 188was prepared following essentially the same procedure but using thereaction conditions of Example 3a in place of part c.

Compound 238 was prepared using the above procedures except propargylbromide was used in place of isobutyl iodide and the resulting6-amino-7-fluoro-4-propargyl-1,4-benzoxazin-3(4H)-one was reacted with3-(difluoromethyl)glutaric anhydride as described in Examples 1 and 2.

EXAMPLE 18:4-(n-propyl)-6-(N-(3-(trifluoromethyl)glutarimido))-1,4-benzoxazoline(Compound 136)

To a slurry of lithium aluminum hydride (1.2 g, 31.6 mmol) in 100 ml THF(fleshly distilled from sodium/benzophenone), was added dropwise via anaddition funnel 6-amino-4-n-propyl-2H-1,4-benzoxazin-3(4H)-one (preparedusing the procedure described in Example 13) (1.89 g, 9.16 mmol)dissolved in 60 ml THF. The slow addition produced a gentle reflux. Uponcompletion of the addition, the reaction was refluxed for 72 hours thencooled to room temperature. Water (1.2 ml) was cautiously added followedby 3.6 ml 15% aqueous NaOH then more water (1.2 ml). After the slightexotherm subsided, the reaction mixture was suction filtered and thesolids were washed with 100 ml THF. The filtrate was concentrated todryness in vacuo to yield 1.43 g (74% yield) of6-amino-4-n-propyl-1,4-benzoxazoline as a brown oil.

The aniline was reacted as described in Examples 1 and 2 to afford thedesired glutarimide.

EXAMPLE 19: N-5'-(3-butynyloxy)-4'-chloro-2'-fluorophenyl-3-(trifluoromethyl)glutarimide(Compound 140)

Potassium carbonate (7.8 g, 56 mmol) was added to a solution of5-amino-2-chloro-4-fluorophenol (3.23 g, 19.9 mmol) in 50 ml methylethyl ketone and the reaction mixture was stirred at room temperaturefor 1 hour. Then 4.2 g (19.9 mmol) 4-phenylsulfonyloxy-1-butyne(prepared from benzenesulfonyl chloride and 3-butyn-1-ol according toknown procedure) was added and the reaction mixture was refluxed for 24hours. The reaction was poured into 50 ml water and the layers wereseparated. The aqueous layer was extracted with EtOAc (1×50 ml) and thecombined organics were washed with H₂ O (3×50 ml), dried over MgSO₄, andconcentrated. The residue was dissolved in 110 ml CH₂ Cl₂ and filteredthrough a short pad of silica gel which was repeatedly rinsed with CH₂Cl₂ (4×100 ml). The combined organics were concentrated in vacuo toyield 0.95 g (22% yield) of the desired product as a brown oil.

The aniline was reacted with 3-(trifluoromethyl)glutaric anhydride asdescribed in Examples 1 and 2 to yield the desired product, m.p. 89°-91° C.

Using the same procedure as used in this example, Compounds 141, 196,216, 231, 232, 234 and 236 were prepared except the appropriatealkylating agent (prepared from methanesulfonyl chloride and an alcoholaccording to known procedures) was used in place of4-phenylsulfonyloxy-1-butyne..

EXAMPLE 20:7-fluoro-4-methoxycarbonyl-6(N-(3-(trifluoromethyl))-glutarimido))-2H-1,4-benzoxazin-3(4H)-one(Compound 142)

To 0.165 g (4.13 mmol) of sodium hydride (washed with hexanes) in 10 mlDMF was added 1.3 g (3.75 mmol) of7-fluoro-6-(N-(3-(trifluoromethyl)-glutarimido))-2H- 1,4-benzoxazin-3(4H)-one (Compound 138) in 20 ml DMF. The reaction was stirred at roomtemperature for 10 minutes before 0.425 g (4.50 mmol) of methylchloroformate was added. The mixture was stirred one hour then pouredonto 50 ml ice/water and extracted with EtOAc (2×50 ml). The organiclayers were combined, dried over anhydrous Na₂ SO₄ and evaporated todryness in vacuo. The residue was chromatographed (silica gel, 1:1hexanes EtOAc) to yield 0.58 g (38% yield) of the desired compound as ayellow oil.

Compound 121, 179 and 200 were prepared using the same procedure exceptthe appropriate alkylating agent was used in place of methylchloroformate.

EXAMPLE 21:N-(3-acetamido-4-methoxyphenyl)-3-(trifluoromethyl)glutarimide (Compound148)

2-Methoxy-5-nitroaniline was purchased and acetylated using HOAc/Ac₂ Oin H₂ O/THF according to known procedures to make2-methoxy-5-nitroacetanilide. This was reduced using catalytichydrogenation (PtO₂, H₂, EtOH) to afford 3-acetamido4-methoxyanilinewhich was reacted as described in Examples 1 and 2 to yield the desiredglutarimide.

EXAMPLE 22:4-methoxymethyl-6-(N-(3-(trifluromoethyl)-glutaramido))-2H-1,4-benzoxazin-3(4H)-one(Compound 151 )

a. 6-nitro-2H-1,4-benzoxazin-3(4H)-one

To a slurry of 2-amino-4-nitrophenol (10.7 g, 69.4 mmol) in 150 ml ofCH₂ Cl₂ was added 19.37 ml (139 mmol) of triethylamine and the mixturewas stirred until homogenous. The reaction flask was then cooled to 0°C. while a solution of chloroacetyl chloride (11.06 ml, 139 mmol) in CH₂Cl₂ (50 ml) was added dropwise. The reaction was allowed to warm to roomtemperature and stirred for 16 hours after which time it was poured onto250 ml of ice. The resulting white precipitate was collected by vacuumfiltration, washed with CH₂ Cl₂ (25 ml) and dried in a vacuum oven at50° C. to yield 20.56 g (90% yield) of the desired intermediate product.

To a solution of 7.82 g (25.6 mmol) ofN,O-bis-(chloromethyl-carbonyl)-2-amino-4-nitrophenol in 25 ml of THFwas added 2.67 ml (51.2 mmol) of 50% NaOH and 10 ml of water. The twophase reaction mixture was stirred at room temperature for 16 hours thenthe solvents were removed in vacuo. The residue was partitioned betweenEt₂ O (100 ml) and water (100 ml) and the layers were separated. Theaqueous layer was extracted sequentially with Et₂ O (2×100 ml) and EtOAc(2×100 ml) and the combined organic phases were dried over MgSO₄ andconcentrated in vacuo to give 1.3 g (26% yield) of the desired product(m.p. 223°-228° C.) as a yellow solid.

b. 4-methoxymethyl-6-nitro-2H-1,4-benzoxazin-3(4H)-one

To 0.976 g (5.02 mmol) of 6-nitro-2H-1,4-benzoxazin-3(4H)-one in 100 mlof chloroform was added 2 ml of dimethoxymethane. Phosphorous pentoxide(5 g, 35 mmol) was added portionwise and the reaction mixture wasstirred at room temperature for 16 hours. TLC analyses showed thestarting material was still present; therefore, additionaldimethoxymethane (2 ml) was added along with several batches ofphosphorous pentoxide (2×1.2 g and 2.0 g) and chloroform (50 ml). Thereaction was stirred for an additional 16 hours then cautiously quenchedwith water (50 ml). The reaction mixture was slowly neutralized with 50ml of 1N NaOH during which time an exotherm occurred. When the reactionmixture had cooled to room temperature, the layers were separated andthe aqueous phase was extracted with chloroform (2×50 ml). The combinedorganic phases were washed with water (2×50 ml), dried over MgSO₄ andconcentrated to afford the desired intermediate product (0.5 g, 42%yield) as a pale yellow solid.

The nitro compound was reduced using the procedure described in Example13c to yield 6-amino-4-methoxymethyl-2H-1,4-benzoxazin-3-one which wasreacted with 3-(trifluoromethyl)glutaric anhydride as described inExamples 1 and 2 to yield the desired product, m.p. 138°-140° C.

Using the procedure as described in this example, except the procedureof 13b was used in place of part b, Compounds 105, 147, 154, 157, 167,211 and 217 were prepared using the appropriate alkylating agent.

EXAMPLE 23:N-(4'-chloro-5'-cyano-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide(Compound 169)

To 1.07 g (3.03 mmol) of N-4'-chloro-2'-fluoro-5'-(N'-oximylphenyl)!-3-(trifluoromethyl)glutarimide(Compound 159) in CH₂ Cl₂ (30 ml) containing 2.0 g anhydrous MgSO₄ wasadded 0.40 g (0.25 ml, 3.36 mmol) of thionyl chloride. The reactionmixture was stirred vigorously for 3 days at room temperature afterwhich time TLC analysis indicated that the starting material was stillpresent. Additional thionyl chloride (0.1 ml) was added and the reactionwas refluxed for 3 hours. TLC now showed that all of the startingmaterial had reacted. The MgSO₄ was filtered and the solvent was removedin vacuo to leave a pale yellow solid (0.90 g, 89% yield) identified byNMR to be the desired cyano compound, m.p. 210°-212° C.

EXAMPLE 24: N- 5'-(isopropylaminiumcarboxylate)-4'-chloro-2'-fluorophenyl!-3-(trifluoromethyl)glutarimide(Compound 177)

ToN-(5'-carboxy-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)-glutarimide(Compound 62) (1.3 g, 3.6 mmol) dissolved in 10 ml EtOAc was added 0.31ml (0.21 g, 3.6 mmol) isopropyl amine. After stirring at roomtemperature for 15 minutes, a white precipitate formed. The fine powderwas filtered and dried in vacuo to afford 0.95 g (75% yield) of thedesired salt, m.p. 168°-173° C. (dec).

EXAMPLE 25: N- 5'-(potassiumcarboxylate)-4'-chloro-2'-fluorophenyl!-3-(trifluoromethyl)glutarimide(Compound 213)

To a suspension of KH (0.6 g of 35% wt dispersion on mineral oil, washed2×5 ml hexanes) in 5 ml of THF was added dropwise a solution ofN-(5'-carboxy4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide(Compound 62) (1.8 g, 5.1 mmol) in 20 ml THF. When the hydrogenevolution subsided, the clear solution was stirred for 10 minutes andthen filtered to remove remaining particulate matter. Concentration ofthe filtrate afforded 1.8 g (90% yield) of the desired potassium salt asa white solid, m.p. 133°-143° C.

EXAMPLE 26: N-3'-(N-methylacetamido)-4'-Chlorophenyl!-3-(trifluoromethyl)glutarimide(Compound 183)

a. N-methyl-2-chloro-5-nitroacetanilide

While being kept under N₂, 3.12 g (78 mmol, 60% dispersion in oil)sodium hydride was washed with pentanes (2×2.5 ml) and then suspended in150 ml anhydrous DMF. To the suspension was added 14.0 g (65.1 mmol)2-chloro-5-nitroacetanilide followed by 50 ml of DMF for rinsing. Thereaction was stirred at room temperature for 15 minutes then methyliodide (20 ml, 45 g, 32 mmol) was added and the reaction was heated to45° C. for 3 hours and stirred at room temperature for another 85 hours.The reaction mixture was poured into 500 ml water and extracted with 500ml EtOAc. The organic layer was washed with water (3×200 ml) and brine(1×200 ml), dried (MgSO₄) and concentrated in vacuo to yield 13.3 g (89%yield) of N-methyl-2-chloro-5-nitroacetanilide as a yellow solid.

b. N-methyl-4-amino-2-chloroacetanilide

To 300 ml absolute ethanol in a Parr bottle was added 12.55 g (54.9mmol) N-methyl-2-chloro-5-nitroacetanilide. After bubbling nitrogenthrough the solution for 15 minutes, 300 mg platinum (IV) oxide wasadded. The flask was placed in a Parr apparatus and shaken for 20minutes under a H₂ atmosphere. The catalyst was removed by filtrationthrough Celite and the filtrate was concentrated in vacuo to give 10.25g (94% yield) of the desired aniline as a yellow solid.

The N-methyl-4-amino-2-chloroacetanilide was reacted with3-(trifluoromethyl)glutaric anhydride as described in Examples 1 and 2to yield the desired product, m.p. 203°-204° C.

EXAMPLE 27: N-4'-chloro-2'-fluoro-5'-(1,3-dioxanyl)phenyl!-3-(trifluoromethyl)glutarimide(Compound 193)

To 3.4 g (10 mmol)N-(4'-chloro-2'-fluoro-5'-formylphenyl)-3-(trifluoromethyl)glutarimide(Compound 94) in 110 ml toluene was added 0.94 g (15 mmol) ethyleneglycol and a catalytic amount of p-toluenesulfonic add monohydrate (0.48g, 2 mmol). The mixture was refluxed for 72 h with removal of water viaa Dean-Stark trap. The solvent was removed in vacuo and the residue waspartitioned between EtOAc and water. The organics were washed with waterand brine, dried over MgSO₄, then filtered and concentrated to leave 4.1g (105 % yield) of an oily taffy containing mostly product by NMRanalysis. Recrystallization from Et₂ O afforded 1.0 g of the 1,3-dioxaneas a pale yellow solid, m.p. 158°-161° C.

EXAMPLE 28:N-(5'-isobutylsulfonyl-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide(Compound 202)

a. 4-chloro-2-fluoro-5-(isobutylthio)acetanilide

Potassium carbonate (26 g, 188 mmol) was added to a solution of5-acetamido-2-chloro-4-fluorothiophenol (11.35 g, 52.4 mmol) in 50 mlanhydrous DMF and the reaction mixture was stirred at room temperaturefor 10 minutes. Then 6.63 ml (57.0 mmol) 1-iodo-2-methylpropane wasadded and the reaction was heated to 50° C. for 18 hours. The reactionwas poured into 200 ml water, then suction filtered to isolate a nearlywhite solid which was dried in vacuo to yield 13.31 g (93 % yield) ofthe alkylated product as an off-white solid.

b. 4-chloro-2-fluoro-5-(isobutylsulfonyl)acetanilide

Meta-chloroperoxybenzoic acid (7.7 g, 36.6 mmol) was added to a solutionof 4-chloro-2-fluoro-5-(isobutylthio)acetanilide (4.9 g, 17.8 mmol) in50 ml CH₂ Cl₂. After the reaction was stirred at room temperature for2.5 hours, additional meta-chloroperoxybenzoic acid (4.6 g, 21.9 mmol)was added and the reaction was stirred for an additional 30 minutesbefore it was poured into 50 ml water. The organic layer was isolatedand washed successively with saturated aqueous sodium bicarbonate (aq.NaHCO₃)(2×50 ml), water (1×50 ml) and aq. NaHCO₃ (2×50 ml). The solventwas removed in vacuo and the residue was dissolved in 100 ml CH₂ Cl₂then washed with 10% aqueous sodium sulfite (1×100 ml) and aq. NaHCO₃(1×100 ml). The organic layer was concentrated to dryness in vacuo toyield 5.5 g of a yellow solid identified by NMR to contain mostly thedesired product. The crude material was used in the next reaction.

c. 4-chloro-2-fluoro-5-(isobutylsulfonyl)aniline

Concentrated hydrochloric acid (16.65 ml, 200 mmol) was added to aslurry of 4-chloro-2-fluoro-5-(isobutylsulfonyl)acetanilide (5.46 g,17.7 mmol) in water (24.85 ml) and ethanol (19.08 ml). The reactionmixture was refluxed for 2 hours, poured onto 200 ml ice and madestrongly basic by the addition of 50% NaOH. The aqueous phase wasextracted with Et₂ O (2×100 ml) and the combined organic layers werewashed with water (1×100 ml) and brine (1×100 ml), dried (Na₂ SO₄) andconcentrated in vacuo. The brown solid obtained (3.8 g, 81% yield) wasshown by NMR to contain the desired aniline as the main component.

The 4-chloro-2-fluoro-5-(isobutylsulfonyl)aniline from above was reactedwith 3-(trifluoromethyl)glutaric anhydride as described in Examples 1and 2 to prepare Compound 202, m.p. 48°-51° C.

EXAMPLE 29:N-(5'-bis-acetamido-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide(Compound 225)

To 100 ml absolute ethanol in a Part bottle was added 3.21 g (8.61 mmol)N-(4'-chloro-2'-fluoro-5'-nitrophenyl)-3-(trifluoromethyl)glutaramicacid (prepared from 4-chloro-2-fluoro-5-nitroaniline and3-(trifluoromethyl)glutaric anhydride using the procedure of Example 1).After bubbling nitrogen through the solution for 15 minutes, 100 mgplatinum (IV) oxide was added. The flask was placed on a Parr apparatusand shaken for 1 hr under an atmosphere of hydrogen. The solids wereremoved by filtration through Celite and the filtrate was concentratedto dryness to give 3.1 g (100% yield) of an off-white solid containingN-(5'-amino-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutaramicacid.

Using the procedure of Example 2,N-(5'-amino-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutaramicacid was converted to Compound 225, m.p. 164°-160° C.

EXAMPLE 30: N-4'-chloro-2'-fluro-5'-(4",4"-dimethyl-2-oxazolin-2-yl)phenyl!-3-(trifluoromethyl)glutarimide(Compound 227)

a. 2-chloro-4-fluoro-5-nitrobenzoyl chloride

To solution of 2-chloro-4-fluoro-5-nitrobenzoic acid (4.0 g, 18 mmol) in65 ml toluene was added 2 drops of DMF followed by 1.8 ml (25 mmol)thionyl chloride. The mixture was heated to reflux for 18 hr, cooled toambient temperature and the solvent was removed in vacuo to afford 4.0 g(93% yield) of a white solid identified by IR and NMR as the desiredbenzoyl chloride. The crude material was used directly in the followingprocedure.

b. N-(1,1-dimethyl-2-hydroxyethyl)-2-chloro-4-fluoro-5-nitrobenzamide

To a cooled (0° C.) solution of 2-amino-2-methyl-1-propanol (2.4 ml, 2.2g, 25 mmol) in CH₂ Cl₂ (10 ml), was added dropwise via an additionfunnel 3.0 g (12 mmol) 2-chloro-4-fluoro-5-nitrobenzoyl chloride in 20ml CH₂ Cl₂. Following the addition, the mixture was allowed to warm toroom temperature and a white precipitate formed. After 1.5 hr, 10 mlwater was added and the mixture was filtered to afford 2.1 g of a paleyellow solid identified by NMR to be the desired product. The filtratewas extracted with EtOAc (3×75 ml) and the combined organic phases werewashed with brine, saturated sodium bicarbonate, again with brine andthen dried over MgSO₄. Concentration gave 1.0 g of additional product(3.1 g, 86% total yield).

c. 2-(2'-chloro-4'-fluoro-5'-nitrophenyl)-4,4-dimethyl-2-oxazoline

To a suspension ofN-(1,1-dimethyl-2-hydroxyethyl)-2-chloro-4-fluoro-5-nitrobenzamide (2.0g, 6.9 mmol) in 30 ml EtOAc was added dropwise 1.6 ml (2.6 g, 22 mmol)thionyl chloride. The resulting clear, yellow solution was stirred atroom temperature for 25 minutes during which time a white precipitateformed. The reaction was then treated with 30 ml 10% NaOH causing aslight exotherm as the solids dissolved. The aqueous phase was extractedwith EtOAc (3×25 ml) and the combined organics were washed with brineand dried (MgSO₄). Concentration afforded 1.85 g (98% yield) of productas a yellow solid.

The 2-(2'-chloro-4'-fluoro-5'-nitrophenyl)-4,4-dimethyl-2-oxazoline wasreduced as described in Example 13c to the corresponding aniline whichwas converted to the glutarimide (Compound 227) using the procedures ofExamples 1 and 2.

EXAMPLE. 31:6-fluoro-3-n-propyl-5-N-(3-(trifluoromethyl)glutarimido))-1,3-benzoxazalin-2(3H)-one(Compound 181)

a. 2-amino-5-fluorophenol

To 500 mg of 10% palladium on carbon in a Parr bottle containing 50 mlof anhydrous ethanol was added a solution of 10 g (64 mmol)5-fluoro-2-nitrophenol in 150 ml ethanol. The flask was evacuated,charged with hydrogen and shaken on a Parr apparatus for 1 hour. Thecatalyst was removed by filtration through Celite® and the filtrate wasevaporated to dryness in vacuo to give 7.54 g (93% yield) of a darksolid.

b. 6-fluoro-1,3-benzoxazolin-2(3H)-one

To 5.0 g (39.3 mmol) 2-amino-5-fluorophenol in 150 ml of CH₂ Cl₂ at 0°C. was added 13.4 (98 mmol) of potassium carbonate and 23 g(47 mmol) of20 wt % phosgene in toluene. After warming to room temperature, thereaction was stirred an additional hour before quenching onto 200 mlice/water. The layers were separated and the aqueous phase was extractedwith EtOAc (1×100 ml) before the organics were combined and dried overNa₂ SO₄. The solvent was removed in vacuo to give 5.76 g (96% yield) ofthe desired product as determined by ¹ H NMR.

c. 6-fluoro-3-n-propyl-1,3-benzoxazolin-2(3H)-one

To 670 mg (16.74 mmol) of hexanes washed sodium hydride in 20 ml DMF wasadded a solution of 2.33 g (15.22 mmol)6-fluoro-1,3-benzoxazolin-2(3H)-one in 40 ml DMF. The reaction wasstirred for 10 minutes before 3.11 g (18.3 mmol) 1-iodopropane was addedand then stirred for 3 hr at room temperature. After quenching onto 50mi of ice/water, the aqueous phase was extracted with EtOAc (2×100 mi).The combined organic layers were washed with water (1×100 ml), driedover Na₂ SO₄ and evaporated to dryness in vacuo to give 2.2 g (75%yield) of the alkylated product as a brown solid.

d. 6-fluoro-5-nitro-3-n-propyl-1,3-benzoxazolin-2(3H)-one

To 2.0 g (10.3 mmol) 6-fluoro-3-n-propyl-1,3-benzoxazolin-2(3H)-one in25 ml acetic anhydride was added dropwise a solution of 2.3 g (24.7mmol) 70% nitric acid in 2 ml glacial acetic acid. After addition wascompleted, the reaction was stirred at room temperature for 2 hours andthen poured onto 50 ml ice/water. The aqueous phase was extracted withEtOAc (2×70 ml) and the combined organics were dried over Na₂ SO₄ andevaporated to dryness in vacuo to give 1.66 g (67 % yield) of thenitrated product as a yellow oil.

The 6-fluoro-5-nitro-3-n-propyl-1,3-benzoxazolin-2(3H)-one preparedabove was reduced to the corresponding aniline following the procedureof Example 17e and the aniline was reacted with3-(trifluoromethyl)glutaric anhydride as described in Examples 1 and 2to yield the desired product, m.p. 148°-152° C.

EXAMPLE32:N-(6-fluoro-1-n-propyl:4H-3,1-benzoxazin-2(1H)-one-7-yl)-3-(trifluoromethyl)glutarimide(Compound 198)

a. 3,1,4-benzoxazin-2(1H)-one

To 4.0 g (32.5 mmol) 2-aminobenzyl alcohol in 200 ml CH₂ Cl₂ at 0° C.was added 11.12 g (81.2 mmol) potassium carbonate followed by 19.3 g(39.0 mmol) 20 wt % phosgene in toluene. The reaction was slowly warmedto room temperature and then stirred for 5 hours. The reaction mixturewas poured into 200 ml saturated NaHCO₃, the layers were separated andthe organic phase was dried over Na₂ SO₄. Concentration gave 4.55 g (84%yield) of the desired product as a white solid.

This 3,1,4-benzoxazin-2(1H)-one was converted to the desired glutarimide(m.p. 158°-160° C.) as described in Examples 17 c-e and Examples 1 and 2except that 1-iodopropane was used in place of isobutyl iodide.

EXAMPLE 33:7-fluoro-4-epoxypropyl-6-N-(3-trifluoromethyl)-glutarimido))-2H-1,4-benzoxazin-3(4H)-One(Compound 239)

To 1.0 g (2.6 mmol)4-allyl-7-fluoro-6-N-(3-trifluoromethyl)-glutarimido))-2H-1,4-benzoxazin-3(4H)-one (Compound 97) in 50 ml CH₂ Cl₂ was added 2.45g (7.8 mmol) m-chloroperoxybenzoic acid. The mixture was stirred at roomtemperature overnight and then poured into 50 ml saturated NaHCO₃. Thelayers were separated and the organic phase was dried over Na₂ SO₄before evaporating to dryness in vacuo. The crude product waschromatographed by preparative thin layer chromatography using 60/40hexanes/EtOAc to give 400 mg (38% yield) of the desired epoxide as adear oil.

Compound 245 was prepared using the above procedure except the startingmaterial wasN-(5'-allyloxy-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide(Compound 9) and the reaction was refluxed overnight in CHCl₃.

EXAMPLE 34: N-4'-chloro-5'-(3,3-dichloroallyloxy)-2'-fluorophenyl!-3-(trifluoromethyl)glutarimide(Compound 244)

Potassium hydroxide (1.95 g, 34.8 mmol) dissolved in 5 ml water wasadded to a solution of 5-amino-2-chloro-4-fluorophenol (5.65 g, 34.8mmol) in 40 ml dimethylsulfoxide. The resulting mixture was stirred atroom temperature for 18 hours, poured into 100 ml water and extractedwith Et₂ O (2×100 ml). The combined organic layers were washed withwater (2×100 ml), dried over Na₂ SO₄, and filtered through a short padof neutral alumina with Et₂ O (3×50 ml rinses). The filtrate wasconcentrated in vacuo to yield 7.56 g (74% yield) of a brown oilcontaining mostly the desired product as identified by ¹ H NMR.

This crude aniline was reacted with 3-(trifluoromethyl)glutaricanhydride as described in Examples 1 and 2 to yield the desired product,m.p. 106°-108° C.

Using the same procedure as used in this example, Compound 240 wasprepared except the alkylating agent was 2-chloro-1-butene. Compound 243was also prepared using this procedure only propargyl bromide was thealkylating agent and the aniline was reacted with3-(difluoromethyl)glutaric anhydride instead of3-(trifluoromethyl)glutaric anhydride.

EXAMPLE 35:N-(4'-chloro-2'-fluoro-5'-nitrophenyl)-3-(trifluoromethyl)glutarimide(Compound 222)

a. 4-chloro-2-fluoro-5-nitroacetanilide

Into a 500 ml, 3-necked round-bottomed flask equipped with a mechanicalstirrer was placed 4-chloro-2-fluoroacetanilide (56.3 g, 0.3 mmol) andconc. H₂ SO₄ (100 ml). While cooling to 0° C., fuming nitric acid (21 g,0.33 mol) was added over 30 minutes and then the reaction mixture waspoured onto 2 liters of ice. When the ice had melted the solid productwas collected by filtration, washed with water and dried in vacuo togive 44 g (63 % yield) of the nitrated material as a tan solid.

b. 4-chloro-2-fluoro-5-nitroaniline

A mixture of 4-chloro-2-fluoro-5-nitroacetanilide (10.88 g, 46.8 mmol),50.4 ml ethanol, 65.7 ml water, and 43.8 ml (526 mmol) concentratedhydrochloric acid was refluxed for one hour and then poured onto 300 mlice. The aqueous phase was made strongly basic by the addition of 50%aqueous sodium hydroxide and was extracted with 2×200 ml Et₂ O. Thecombined organic layers were washed with water (200 ml) and brine (200ml) then dried over Na₂ SO₄ and concentrated to dryness in vacuo to give8 g (90 % yield) of the desired aniline as a yellow solid.

This aniline was reacted with 3-(trifluoromethyl)glutaric anhydride asdescribed in Examples 1 and 2 to yield the desired glutarimide, m.p.164°-167 ° C.

EXAMPLE 36:N-(5'-isobutylsulfoxy-4'-chloro-2'-fluorophenyl)-3-(trifluoromethyl)glutarimide(Compound 246)

To a solution of 4-chloro-2-fluoro-5-(isobutylthio)acetanilide (seeExample 28a) (1.04 g, 3.8 mmol) in 30 ml ethanol, cooled to 0° C., wasadded sodium periodate (1.29 g, 6.0 mmol) in 6 ml water. The reactionwas allowed to warm to room temperature and was stirred for 18 hours.The solids were removed by suction filtration and the filtrate wasdissolved in 75 ml CH₂ Cl₂ and then washed with water (50 ml). Theorganic layer was dried over Na₂ SO₄ and concentrated to dryness toyield 1 g (90 % yield) of the desired sulfoxide as a white solid.

The procedure of Example 28c was used to prepare the correspondinganiline which was reacted with 3-(trifluoromethyl)glutaric anhydride asdescribed in Example 1 and 2 to give the desired glutarimide, m.p.133°-134° C.

The compounds of the present invention are broad spectrum herbicides andmay be advantageously employed to control selectively monocot and/ordicot weeds in agronomic and horticultural crops, forestry, orchards,turf, vines or for total weed control.

The compounds of the present invention are selective or non-selective,depending on the rate applied, the combination of plants to which theyare applied and whether they are applied pre- or postemergent. Suchvariables are understood by those skilled in the art. At higher dosagerates they tend to be non-selective, while at lower dosage rates theytend to be selective. For example, the ether and thioether glutarimidecompounds described above are active both preemergence and postemergenceand have shown postemergent control of dicots in wheat; the esterglutarimides have shown preemergent and postemergent control of monocotsand dicots, generally requiring lower doses to control dicots than tocontrol monocots; and the heterocyclic glutarimides have shownselectivity preemergence and/or postemergence in crops such as, but notlimited to, wheat, corn, rice, soybeans, sunflower, peanuts and cotton.

The present glutarimides may be applied in any amount which will givethe required control of the undesired plants. Generally a rate ofapplication of the herbicides of the invention is from about 0.0001 toabout 12 pounds per acre and preferably from about 0.001 to about 5pounds of the glutarimide compound per acre. Most preferably a rate fromabout 0.002 to about 2 pounds of the glutarimide per acre is used.

The compounds of the present invention are useful both as preemergenceand as postemergence herbicides. Preemergence herbicides may be appliedto the soil surface or incorporated into the soil. Postemergenceherbicides are those which are applied after the plants have emerged andduring their growth period. The glutarimides of the present inventionmay be applied to the soil surface prior to plant emergence orincorporated into the soil or other growth medium prior to planting.This incorporation can be carried out by any convenient means, includingby simply mixing with the soil, by applying the glutarimide to thesurface of the soil and then disking or dragging into the soil to thedesired depth, or by employing a liquid carrier to accomplish thenecessary penetration and impregnation.

A glutarimide of the present invention can be applied postemergence tothe growth medium or to plants to be treated either by itself, or, as isgenerally done, as a component in a herbicidal composition orformulation which also comprises an agronomically acceptable carrier.The concentration of the glutarimide in the herbicidal composition canvary from about 1% to about 98%.

By agronomically acceptable carrier is meant any substance which can beused to dissolve, disperse or diffuse a herbicidal compound in thecomposition without impairing the effectiveness of the herbicidalcompound and which by itself has no detrimental effect on the soil,equipment, crops or agronomic environment. Mixtures of the glutarimidesof the present invention may also be used in any of these herbicidalformulations. The herbicidal compositions of the invention can be eithersolid or liquid formulations or solutions. For example, the glutarimidescan be formulated as wettable powders, solutions, emulsifiableconcentrates, dusts, granular formulations, aerosols, water dispersablegranular formulations or flowable concentrates as is known to oneskilled in the art. In such formulations, the compounds are extendedwith a liquid or solid carrier and, when desired, suitable surfactantsor emulsifiers are incorporated. Examples of solvents which are usefulin the practice of this invention include water, alcohols, ketones,aromatic hydrocarbons, halogenated hydrocarbons, dimethylformamide,dioxane, dimethyl sulfoxide and the like. Mixtures of these solvents canalso be used.

It is usually desirable, particularly in postemergence applications, toinclude adjuvants such as wetting agents, spreading agents, dispersingagents, sticking agents, adhesives and the like, in accordance withagricultural practices. Examples of adjuvants which are commonly used inthe art can be found in the John W. McCutcheon, Inc. publication"Detergents and Emulsifiers Annual."

The glutarimides of the present invention can also be mixed withfertilizers or fertilizing materials before their application. In onetype of solid fertilizing composition in which the glutarimides may beused, particles of a fertilizer or fertilizing ingredients, such asammonium sulfate, ammonium nitrate or ammonium phosphate can be coatedwith one or more of the glutarimides. The solid glutarimide and solidfertilizing material may also be admixed in blending or mixingequipment, or they can be incorporated with fertilizers in granularformulations. Any relative proportion of glutarimide and fertilizer canbe used which is suitable for the crops and weeds to be treated.

The glutarimides of the present invention may be applied as herbicidalsprays by methods commonly employed, such as conventional high-gallonagehydraulic sprays, low gallonage sprays, air blast spray, aerial spraysand dusts. For some applications two or more of the glutarimides of theinstant invention may be combined, thereby providing additionaladvantages and effectiveness. When mixtures of the glutarimides of theinvention are used, the relative proportion of each compound used willdepend on the relative efficacy of the compounds in the mixture withrespect to the plants to be treated.

For some applications, one or more other herbicides may be added to theglutarimides of the present invention, thereby providing additionaladvantages and effectiveness. When mixtures of herbicides are employed,the relative proportions which are used will depend upon the relativeefficacy of compounds in the mixture with respect to the plants to betreated. Examples of other herbicides which can be combined with theglutarimides of the present invention include:

Carboxylic Acids and Derivatives

2,3,6-trichlorobenzoic acid and its salts;

2,3,5,6-tetrachlorobenzoic acid and its salts;

2-methoxy-3,5,6-trichlorobenzoic acid and its salts;

2-methoxy-3,6-dichlorobenzoic acid and its salts;

2-methyl-3,6-dichlorobenzoic acid and its salts;

2,3-dichloro-6-methylbenzoic acid and its salts;

2,4-dichlorophenoxyacetic acid and its salts and esters;

2,4,5-trichlorophenoxyacetic acid and its salts and esters;

2-methyl-4-chlorophenoxyacetic acid and its salts and esters;

2-(2,4,5-trichlorophenoxy)propionic acid and its salts and esters;

4-(2,4-dichlorophenoxy)butyric acid and its salts and esters;

4-(2-methyl-4-chlorophenoxy)butyric acid and its salts and esters;

2,3,6-trichlorophenylacetic acid and its salts;

3,6-endoxohexahydrophthalic acid and its salts;

dimethyl 2,3,5,6-tetrachloroterephthalate;

trichloroacetic acid and its salts;

2,2-dichloropropiordc acid and its salts;

2,3-dichloroisobutyric acid and its salts;

isopropylammonium2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinate;

2-4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl!-3-quinolinecarboxylicacid;

m-toluic acid, 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-, methylester and p-toluic acid,6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-, methyl ester;

N-(phosphonomethyl)glycine, isopropylammonium salt;

3,5,6-trichloro-(2-pyridinyl)oxy!acetic acid;

3,7-dichloro-8-quinolinecarboxylic acid;

ammonium dl-homoalanin-4-yl(methyl)phosphinate;

Carbamic Add Derivatives

ethyl N,N-di(n-propyl)thiolcarbamate;

n-propyl N,N-di(n-propyl)thiolcarbamate;

ethyl N-ethyl-N-(n-butyl)thiolcarbamate;

n-propyl N-ethyl-N-(n-butyl)thiolcarbamate;

2-chloroallyl N,N-diethyldithiocarbamate;

N-methyldithiocarbamic acid salts;

ethyl 1-hexamethyleneiminecarbothiolate;

isopropyl N-phenylcarbamate;

isopropyl N-(m-chlorophenyl)carbamate;

4-chloro-2-butynyl-N-(m-chlorophenyl)carbamate;

methyl N-(3,4-dichlorophenyl)carbamate;

dinitro-o-(sec-butyl)phenol and its salts;

pentachlorophenol and its salts;

S-(4-chlorobenzyl)-N ,N-diethylthiolcarbamate;

Substituted Ureas

2-chloro-N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl!-benzenesulfonamide;

3-(3,4-dichlorophenyl)-1,1-dimethylurea;

3-phenyl-1,1-dimethylurea;

3-(3,4-dichlorophenyl)-3-methoxy-1,1-dimethylurea;

3-(4-chlorophenyl)-3-methoxy-1,1-dimethylurea;

3-(3,4-dichlorophenyl)-1-n-butyl-1-methylurea;

3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea;

3-(4-chlorophenyl)-1-methoxy-1-methylurea;

3-(3,4-dichlorophenyl)-1,1,3-trimethylurea;

3-(3,4-dichlorophenyl)diethylurea;

dichloral urea;

methyl 2-(4,6-dimethyl-2-pyrimidinyl)amino!-carbonyl!amino!sulfonyl!benzoate;

N-((6-methoxy-4-methyl-1,3,5-triazin-2-yl)aminocarbonyl)-2-(2-chloroethoxy)benzenesulfonamide;

2-(4-chloro-6-methoxypyrimidine-2-yl)aminocarbonyl!amino!-sulfonyl!benzoicacid, ethyl ester;

methyl 2-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino!-carbonyl!amino!sulfonyl!benzoate;

methyl 3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino!carbonyl!-amino!sulfonyl!-2-thiophenecarboxylate;

methyl 2-(4,6-dimethoxypyrimidin-2-yl)amino!carbonyl!-amino!sulfonyl!methyl!benzoate;

methyl 2-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)methylamino!-carbonyl!amino!sulfonyl!benzoate;

Substituted Triazines

2-chloro-4,6-bis(ethylamino)-s-triazine;

2-chloro-4-ethylamino-6-isopropylamino-s-triazine;

2-chloro-4,6-bis(methoxy-n-propylamino)-s-triazine;

2-methoxy-4,6-bis(isopropylamino)-s-triazine;

2-chloro-4-ethylamino-6-(3-methoxy-n-propylamino)-s-triazine;

2-methylmercapto-4,6-bis(isopropylamino)-s-triazine;

2-methylmercapto-4,6-bis(ethylamino)-s-triazine;

2-methylmercapto-4-ethylamino-6-isopropylamino-s-triazine;

2-chloro-4,6-bis(isopropylamino)-s-triazine;

2-methoxy-4,6-bis(ethylamino)-s-triazine;

2-methoxy-4-ethylamino-6-isopropylamino-s-triazine;

2-methylmercapto-4-(2-methoxyethylamino)-6-isopropylamino-s-triazine;

4-amino-6-(t-butyl)-3-(methylthio)-1,2,4-triazine-5(4H)-one;

Diphenyl Ether Derivatives

2,4-dichloro-4'-nitrodiphenyl ether;

2,4,6-trichloro-4'-nitrodiphenyl ether;

2,4-dichloro-6-fluoro-4'-nitrodiphenyl ether;

3-methyl-4'-nitrodiphenyl ether;

3,5-dimethyl-4'-nitrodiphenyl ether;

2,4'-dinitro-4-(trifluoromethyl)diphenyl ether;

2,4-dichloro-3'-methoxy-4'-nitrodiphenyl ether;

sodium 5-(2-chloro-4-(trifluoromethyl)phenoxy)-2-nitrobenzoate;

2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene;

1-(carboethoxy)ethyl5-2-chloro-4-(trifluoromethyl)-phenoxy!-2-nitrobenzoate;

5-2-chloro-4-(trifluoromethyl)phenoxy!-N-(methylsulphonyl)-2-nitrobenzamide;

Anilides

2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide;

2-chloro-2',6'-diethyl-N-(2-propyloxyethyl)acetanilide;

N-(3,4-dichlorophenyl)propionamide;

N-(3,4-dichlorophenyl)methacrylamide;

N-(3-chloro-4-methylphenyl)-2-methylpentanamide;

N-(3,4-dichlorophenyl)trimethylacetamide;

N-(3,4-dichlorophenyl)-alpha,alpha-dimethylvaleramide;

N-isopropyl-N-phenylchloroacetamide;

N-n-butoxymethyl-N-(2,6-diethylphenyl)chloroacetamide;

N-methoxymethyl-N-(2,6-diethylphenyl)chloroacetamide;

Oxyphenoxy Herbicides

2-(4-(2,4-dichlorophenoxy)phenoxy)methyl propionate;

methyl2-(4-(3-chloro-5-(trifluoromethyl)-2-pyridinyloxy)phenoxy)propanoate;

butyl (R)-2- 4- 5-(trifluoromethyl)-2-pyridinyloxy!-phenoxy!propionate;

ethyl 2- 4- (6-chloro-2-benzoxazolyl)oxy!phenoxy!propanoate;

butyl 2- 4- 5-(trifluoromethyl)-2-pyridinyl!oxy!phenoxy!propionate;

2- 4- (6-chloro-2-quinoxalinyl)oxy!phenoxy!propionic acid, ethyl ester;

Uracils

5-bromo-3-s-butyl-6-methyluracil;

5-bromo-3-cyclohexyl-1,6-dimethyluracil;

3-cyclohexyl-5,6-trimethyleneuracil;

5-bromo-3-isopropyl-6-methyluracil;

3-tert-butyl-5-chloro-6-methyluracil;

Nitriles

2,6-dichlorobenzonitrile; diphenylacetonitrile;

3,5-dibromo-4-hydroxybenzonitrile;

3,5-diiodo-4-hydroxybenzonitrile;

Other Organic Herbicides

2-chloro-N,N-diallylacetamide;

N-(1,1-dimethyl-2-propynyl)-3,5-dichlorobenzamide;

maleic hydrazide;

3-amino-1,2,4-triazole;

monosodium methanearsonate;

disodium methanearsonate;

N,N-dimethyl-alpha,alpha-diphenylacetamide;

N,N-di(n-propyl)-2,6-dinitro-4-(trifluoromethyl)aniline;

N,N-di(n-propyl)-2,6-dinitro-4-methylaniline;

N,N-di(n-propyl)-2,6-dinitro-4-methylsulfonylaniline;

O-(2,4-dichlorophenyl)-O-methyl isopropylphosphoramidothioate;

4-amino-3,5,6-trichloropicolinic acid;

2,3-dichloro-1,4-naphthoquinone;

di(methoxythiocarbonyl)disulfide;

3-(1-methylethyl)-1H-2,1,3-benzothiadiazin-(4)3H-one-2,2-dioxide;

6,7-dihydrodipyridol 1,2-a:2',1'-c!pyrazidiium salts;

1,1'-dimethyl-4,4'-bipyridinium salts;

3,4,5,6-tetrahydro-3,5-dimethyl-2-thio-2H-1,3,5-thiadiazine;

2- 1-(ethoxyimino)butyl!-5-2-(ethylthio)propyl!-3-hydroxy-2-cyclohexen-1-one;

2-(2-chlorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone;

N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzamide;

4-chloro-5-(methylamino)-2-(α,α,α-trifluoro-m-toluyl)-3(2H)-pyridazinone;

2-(3,5-dichlorophenyl)-2-(2,2,2-trichloromethyl)oxirane.

The herbicidal activity of glutarimides of the present invention towardsa number of common weeds was evaluated using a greenhouse method oftesting. Using the procedures described below, the glutarimides of thepresent invention were evaluated for control of weeds selected from thefollowing:

    ______________________________________    Monocots    Barnyardgrass (BYG)                      Echinochloa crus-galli    Crabgrass (CRB)   Digitaria sanguinilis    Foxtail (FOX)     Setaria viridis    Johnsongrass (JON)                      Sorghum halepense    Meadow Foxtail (MF)                      Alopecurus pratensis    Nutsedge (NUT)    Cyperus esculentus    Wild Oat (WO)     Avena fatua    Dicots    Beggartick (BID)  Bidens pilosa    Cocklebur (CKL)   Xanthium strumarium    Morningglory (MG) Ipomoea lacunosa    Nightshade (NS)   Solanum nigrum    Pigweed (PIG)     Amaranthus retroflexus    Smartweed (SMT)   Polygonum lapathifolium    Velvetleaf (VEL)  Abutilon theophrasti    ______________________________________

The following test procedure was employed. Seeds of selected plants wereplanted in flats or pots. For preemergence tests, immediately afterplanting, the test compound was sprayed directly onto the soil surface.The flats or pots were then watered by overhead irrigation. Forpostemergence tests, the seeds were allowed to germinate and grow for 10to 21 days. Each series of test plants were selected for uniformity,size and stage of development. The test plants were then treated withthe test compound. The plants for postemergence tests were watered bysubirrigation only.

The compound to be evaluated was dissolved in an appropriate solvent,usually acetone, and sprayed over the flats or pots using a carriervolume equivalent to 25 or 50 gallons per acre at the rate ofapplication in pounds per acre (lb./A) specified in the table. About tento twenty-one days after application of the test compound, the state ofgrowth of the plant was observed. Each species was evaluated on a scaleof 0-100 in which 0 equals no activity and 100 equals total control. Thefollowing tables (Tables VI and VII) shows the results obtained for thetest compounds at the stated rate of application.

                                      TABLE VI    __________________________________________________________________________    HERBICIDAL ACTIVITY    Com-    pound        Rate    No. (lb./A)            Type                CKL                   MG PIG                         VEL                            SMT                               BYG                                  FOX                                     JON                                        NUT                                           WO    __________________________________________________________________________     1. 2   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        100                                           100        2   POST                100                   100                      100                         100                            --*                               100                                  100                                     99 98 100     2. 2   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        100                                           100        2   POST                100                   100                      100                         100                            -- 100                                  100                                     99 5  100     3. 2   PRE 100                   100                      100                         100                            -- 100                                  100                                     100                                        80 99        2   POST                100                   100                      100                         100                            100                               100                                  100                                     99 80 90     4. 2   PRE 0  100                      100                         100                            100                               100                                  100                                     85 10 90        2   POST                99 100                      100                         100                            100                               100                                  100                                     65 10 70     5. 1   PRE 71 100                      100                         100                            100                               100                                  100                                     100                                        65 100        1   POST                100                   100                      100                         100                            100                               99 100                                     90 90 100     6. 1   PRE 100                   100                      100                         100                            100                               100                                  100                                     98 100                                           100        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        0  60     7. 1   PRE 100                   100                      100                         100                            100                               99 100                                     100                                        0  100        1   POST                100                   99 100                         100                            100                               100                                  100                                     100                                        0  35     8. 1   PRE 0  90 0  100                            15 41 98 0  0  0        1   POST                45 15 100                         100                            100                               45 75 15 0  35     9. 2   PRE 75 100                      100                         100                            -- 100                                  100                                     90 80 90        2   POST                100                   100                      100                         100                            100                               100                                  100                                     70 65 100    10. 1   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        30 100        1   POST                71 100                      100                         100                            100                               100                                  100                                     100                                        100                                           100    11. 1   PRE 0  0  0  100                            0  0  21 15 0  0        1   POST                70 60 95 100                            100                               15 25 5  0  0    12. 1   PRE 0  100                      100                         100                            100                               99 100                                     95 80 98        1   POST                100                   100                      100                         100                            100                               95 100                                     98 10 100    13. 4   PRE -- 0  0  0  0  0  0  0  0  0        4   POST                15 45 100                         45 15 10 30 10 0  10    14. 4   PRE 80 100                      100                         100                            100                               100                                  100                                     100                                        100                                           100        4   POST                0  100                      100                         100                            0  100                                  100                                     98 45 98    15. 4   PRE 0  0  100                         100                            100                               10 100                                     20 0  0        4   POST                5  35 20 60 10 15 90 10 0  5    16. 4   PRE 0  95 100                         100                            0  0  95 0  0  27        4   POST                0  80 100                         100                            10 20 100                                     10 0  10    17. 4   PRE 100                   100                      100                         100                            100                               100                                  100                                     98 100                                           75        4   POST                100                   100                      100                         100                            100                               100                                  99 25 65 65    18. 4   PRE 0  100                      100                         100                            50 100                                  100                                     70 98 65        4   POST                35 55 100                         100                            98 85 100                                     10 80 10    19. 4   PRE 0  90 100                         100                            0  45 100                                     0  20 25        4   POST                100                   90 98 100                            20 100                                  100                                     25 10 85    20. 4   PRE 0  0  100                         100                            50 0  0  0  0  0        4   POST                100                   20 100                         100                            100                               90 100                                     20 10 15    21. 4   PRE 31 61 100                         100                            100                               0  100                                     0  0  0        4   POST                15 10 100                         95 100                               0  0  0  0  0    22. 4   PRE 98 100                      100                         100                            100                               100                                  100                                     80 75 51        4   POST                55 55 100                         100                            85 20 100                                     5  45 5    23. 4   PRE 0  0  100                         100                            0  90 100                                     15 0  0        4   POST                0  0  25 0  0  0  0  0  0  0    24. 1   PRE 0  100                      100                         100                            100                               70 100                                     85 70 10        1   POST                100                   99 100                         100                            100                               40 100                                     20 10 20    25. 1   PRE 0  100                      100                         100                            100                               99 100                                     85 85 90        1   POST                40 100                      100                         100                            100                               100                                  100                                     30 10 25    26. 4   PRE 0  0  100                         15 0  15 100                                     20 0  0        4   POST                15 15 90 100                            35 0  15 5  0  0    27. 4   PRE 0  0  100                         20 -- 75 100                                     51 0  20        4   POST                0  70 100                         35 100                               70 45 15 0  15    28. 4   PRE 0  90 100                         100                            100                               98 100                                     95 25 85        4   POST                0  5  100                         100                            100                               5  5  0  0  0    29. 2   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        100                                           100        2   POST                100                   100                      100                         100                            100                               100                                  100                                     85 95 99    30. 1   PRE 0  100                      100                         100                            100                               100                                  100                                     80 85 80        1   POST                45 100                      90 100                            100                               95 95 40 0  45    31. 4   PRE 0  0  100                         100                            -- 50 100                                     85 -- 0        4   POST                0  0  5  0  -- 0  0  0  0  0    32. 4   PRE 0  15 100                         100                            80 75 100                                     0  60 21        4   POST                0  5  10 5  10 0  0  0  0  0    34. 4   PRE 0  5  100                         100                            0  75 100                                     5  5  0        4   POST                5  45 90 100                            98 20 15 5  0  5    35. 4   PRE 0  0  -- 100                            0  0  21 0  0  0        4   POST                0  10 0  0  0  0  0  0  0  0    36. 4   PRE 0  0  0  0  0  0  0  0  0  0        4   POST                0  20 15 25 0  10 5  0  0  0    37. 4   PRE 0  0  0  21 51 21 51 51 51 61        4   POST                0  0  0  0  0  0  0  0  0  0    38. 1   PRE 0  0  100                         100                            100                               60 100                                     25 0  15        1   POST                5  10 15 10 10 0  0  0  0  0    39. 4   PRE 0  0  -- 45 0  0  0  0  0  0        4   POST                0  0  0  0  0  0  0  0  0  0    40. 4   PRE 0  0  0  0  0  0  0  0  0  0        4   POST                0  0  0  0  10 0  0  0  0  0    41. 1   PRE 0  100                      -- 100                            100                               98 100                                     100                                        0  98        1   POST                100                   70 100                         100                            100                               80 75 15 10 65    42. 4   PRE 0  15 0  100                            70 0  85 0  10 0        4   POST                15 25 10 5  10 10 25 0  0  5    43. 2   PRE 100                   100                      100                         100                            100                               100                                  100                                     90 100                                           100        2   POST                100                   100                      100                         100                            100                               100                                  100                                     90 100                                           100    44. 1   PRE 0  50 100                         100                            100                               100                                  100                                     15 100                                           75        1   POST                100                   100                      100                         100                            100                               80 100                                     70 0  30    45. 1   PRE 100                   100                      100                         100                            100                               100                                  100                                     99 55 100        1   POST                100                   100                      100                         100                            100                               99 85 70 20 85    46. 1   PRE 15 70 100                         100                            100                               100                                  100                                     90 100                                           80        1   POST                100                   80 100                         100                            100                               80 60 45 10 25    47. 1   PRE 10 100                      100                         100                            100                               98 100                                     45 11 90        1   POST                90 90 100                         100                            100                               20 5  5  5  15    48. 1   PRE 0  90 100                         100                            100                               85 100                                     15 0  60        1   POST                95 90 100                         100                            100                               25 10 10 0  10    49. 4   PRE 0  0  -- 90 20 0  15 0  0  0        4   POST                0  10 0  0  -- 0  0  0  0  0    50. 1   PRE 0  100                      100                         100                            100                               95 100                                     80 0  10        1   POST                100                   100                      70 100                            100                               80 40 30 0  20    51. 1   PRE 100                   100                      100                         100                            100                               100                                  100                                     80 65 100        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        45 100    53. 1   PRE 61 100                      100                         100                            100                               25 100                                     75 20 15        1   POST                100                   20 98 100                            95 10 35 0  0  10    54. 1   PRE 0  0  0  0  0  0  0  0  0  0        1   POST                0  100                      100                         100                            100                               95 15 0  0  10    55. 4   PRE 0  85 100                         20 90 0  15 0  0  0        4   POST                80 100                      100                         100                            100                               45 40 5  0  5    56. 1   PRE 0  0  -- 0  -- 0  0  0  0  0        1   POST                80 100                      100                         100                            100                               100                                  35 90 10 60    57. 1   PRE 0  100                      0  100                            100                               0  0  -- 0  0        1   POST                100                   100                      100                         100                            90 20 25 0  0  0    58. 1   PRE 0  20 100                         100                            25 0  0  -- 0  0        1   POST                5  80 65 70 100                               0  0  25 0  0    59. 1   PRE 0  0  100                         100                            0  0  0  0  0  0        1   POST                100                   100                      100                         75 100                               15 70 10 0  0    60. 1   PRE 51 100                      100                         100                            100                               70 100                                     90 0  0        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        20 25    61. 1   PRE 0  0  0  50 0  0  85 0  0  0        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        30 45    62. 1   PRE 0  0  0  0  0  0  0  0  0  0        1   POST                98 70 100                         100                            85 90 100                                     35 0  0    63. 4   PRE 0  0  0  100                            100                               0  75 0  0  10        4   POST                5  0  0  0  0  0  0  0  0  0    64. 2   PRE 0  0  0  0  0  0  0  0  0  0        2   POST                -- 0  85 15 100                               15 0  0  0  0    65. 2   PRE -- 0  100                         0  0  0  0  0  0  0        2   POST                30 30 100                         90 100                               0  10 10 0  0    66. 4   PRE 0  0  0  25 0  0  5  0  0  0        4   POST                0  0  10 35 0  0  0  0  0  0    67. 4   PRE -- 0  100                         0  100                               -- 0  90 0  0        4   POST                0  5  5  10 0  0  0  0  0  5    68. 4   PRE 0  0  -- 100                            25 0  5  0  0  0        4   POST                0  0  0  0  0  0  0  0  0  0    69. 4   PRE 0  0  0  100                            0  90 0  0  0  0        4   POST                0  15 5  0  5  0  0  0  0  0    70. 4   PRE 0  0  -- 100                            0  0  11 0  0  0        4   POST                0  5  0  0  0  0  0  0  0  0    71. 1   PRE 36 100                      100                         100                            -- 80 100                                     25 0  0        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        60 75    72. 1   PRE 0  100                      -- 100                            -- 90 100                                     0  0  60        1   POST                100                   100                      100                         100                            100                               95 100                                     85 5  65    73. 1   PRE 0  95 -- 0  -- 75 100                                     0  0  20        1   POST                60 20 80 100                            100                               15 80 5  15 5    74. 1   PRE 0  0  0  100                            0  0  15 5  0  0        1   POST                100                   100                      100                         100                            100                               100                                  100                                     95 10 25    75. 1   PRE 15 100                      100                         100                            100                               70 100                                     60 0  70        1   POST                100                   100                      100                         100                            100                               95 100                                     75 0  10    76. 1   PRE 0  100                      100                         100                            100                               100                                  100                                     90 35 90        1   POST                55 100                      100                         100                            25 80 95 80 10 40    77. 4   PRE 30 100                      100                         100                            100                               99 100                                     80 0  55        4   POST                45 70 100                         95 100                               15 40 0  0  0    78. 4   PRE 90 100                      100                         100                            100                               100                                  100                                     99 45 75        4   POST                25 20 20 100                            100                               0  25 0  0  0    79. 4   PRE 0  100                      100                         100                            100                               99 95 95 0  15        4   POST                35 50 55 95 100                               0  0  10 10 10    80. 4   PRE 90 100                      100                         100                            100                               100                                  100                                     100                                        15 99        4   POST                60 85 100                         100                            100                               100                                  100                                     85 30 45    81. 1   PRE 80 100                      100                         100                            100                               100                                  100                                     100                                        75 90        1   POST                55 100                      100                         100                            98 30 60 15 20 30    82. 1   PRE 0  100                      100                         100                            100                               100                                  100                                     98 25 85        1   POST                100                   100                      100                         100                            100                               100                                  100                                     95 35 80    83. 1   PRE 25 100                      100                         100                            100                               100                                  100                                     95 25 50        1   POST                100                   100                      100                         100                            100                               95 100                                     70 20 0    84. 4   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        70 98        4   POST                30 100                      100                         100                            100                               15 70 100                                        100                                           70    85. 1   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        100                                           100        1   POST                60 100                      100                         100                            100                               0  100                                     100                                        0  0    86. 4   PRE 0  0  -- 0  0  0  20 0  0  0        4   POST                0  0  100                         99 0  80 100                                     70 0  10    87. 4   PRE 30 100                      100                         100                            100                               100                                  100                                     100                                        98 90        4   POST                45 10 100                         100                            100                               50 65 55 35 15    88. 1   PRE 80 100                      100                         100                            100                               100                                  100                                     100                                        15 95        1   POST                70 100                      90 100                            100                               25 50 50 0  0    89.   0.3            PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        80 100          0.3            POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        85 100    90.   0.3            PRE 60 100                      100                         100                            100                               55 100                                     60 0  0          0.3            POST                100                   100                      100                         100                            100                               20 35 25 15 25    91. 4   PRE 0  0  100                         60 100                               0  100                                     15 0  20        4   POST                5  0  20 0  0  0  0  0  0  0    92. 1   PRE 95 15 100                         100                            100                               100                                  100                                     100                                        100                                           80        1   POST                100                   75 100                         100                            100                               100                                  100                                     95 100                                           40    96. 1   PRE 100                   100                      -- 100                            100                               100                                  100                                     100                                        100                                           100        1   POST                75 100                      100                         100                            100                               85 90 35 100                                           0    97. 1   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        100                                           100        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        100                                           75    98. 1   PRE 100                   100                      -- 100                            100                               100                                  100                                     100                                        100                                           100        1   POST                98 100                      100                         100                            100                               100                                  100                                     100                                        100                                           95    99. 4   PRE 0  0  0  20 -- 0  45 0  0  0        4   POST                0  25 45 70 0  5  10 0  0  0    100.        1   PRE 0  20 100                         100                            65 0  30 10 0  0        1   POST                35 90 100                         100                            65 25 15 15 10 15    101.        1   PRE 0  0  100                         50 100                               0  0  0  0  0        1   POST                20 25 10 65 100                               25 0  0  0  0    102.        1   PRE 100                   100                      100                         100                            100                               90 100                                     85 0  15        1   POST                100                   100                      100                         100                            100                               100                                  100                                     60 10 0    103.        1   PRE 0  0  100                         90 99 0  25 0  0  0        1   POST                100                   98 100                         100                            100                               50 98 20 0  0    104.        1   PRE 100                   100                      100                         100                            100                               95 100                                     95 0  50        1   POST                100                   100                      100                         100                            100                               40 95 10 0  0    105.        1   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        65 100        1   POST                85 100                      100                         100                            100                               55 85 85 35 --    106.        1   PRE 0  50 100                         100                            100                               85 100                                     60 0  95        1   POST                10 10 70 100                            60 15 30 10 0  15    107.        1   PRE 0  90 100                         100                            100                               90 100                                     60 0  75        1   POST                15 30 100                         100                            95 15 20 15 0  15    108.        1   PRE 10 20 100                         100                            100                               55 100                                     70 0  10        1   POST                30 65 35 100                            100                               0  0  10 15 15    109.        1   PRE 0  0  100                         10 0  55 10 0  0  0        1   POST                40 65 10 99 95 0  0  0  0  0    110.        1   PRE 10 20 100                         100                            100                               90 100                                     30 5  10        1   POST                95 100                      100                         100                            90 100                                  100                                     85 20 15    111.        1   PRE 100                   95 100                         100                            100                               100                                  100                                     90 20 95        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        80 95    112.        1   PRE 15 90 100                         100                            100                               100                                  100                                     45 10 45        1   POST                100                   100                      100                         100                            100                               100                                  100                                     20 80 100    113.        1   PRE 50 85 -- 100                            100                               95 100                                     75 0  10        1   POST                75 90 100                         100                            100                               100                                  100                                     30 15 90    114.        1   PRE 90 100                      100                         100                            100                               100                                  100                                     95 25 99        1   POST                50 35 95 95 99 70 100                                     70 0  45    115.        1   PRE 75 65 100                         100                            100                               100                                  100                                     100                                        35 80        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        15 80    116.        1   PRE 100                   100                      100                         100                            100                               98 100                                     85 15 98        1   POST                95 95 100                         100                            100                               100                                  100                                     65 15 80    117.        1   PRE 100                   100                      100                         100                            100                               100                                  100                                     99 65 100        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        55 100    118.        1   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        100                                           100        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        45 100    119.        4   PRE 10 0  100                         100                            0  85 100                                     45 0  15        4   POST                0  0  0  0  0  0  0  0  0  0    120.        4   PRE 0  0  95 100                            85 95 100                                     80 0  15        4   POST                0  0  0  0  0  0  0  0  0  0    122.        1   PRE 100                   100                      100                         100                            100                               100                                  100                                     100                                        100                                           99        1   POST                100                   100                      100                         100                            100                               100                                  100                                     100                                        100                                           100    124.        1   PRE 85 100                      100                         100                            100                               100                                  -- 100                                        100                                           70        1   POST                10 0  100                         100                            100                               35 15 100                                        35 0    125.        4   PRE 0  0  100                         100                            55 95 100                                     -- 10 10        4   POST                0  0  70 100                            0  0  20 0  0  0    126.        1   PRE 95 100                      -- 100                            100                               100                                  100                                     100                                        100                                           100        1   POST                65 35 30 100                            70 75 100                                     85 0  0    128.        1   PRE 100                   100                      -- 100                            100                               100                                  100                                     100                                        98 100        1   POST                55 98 100                         100                            100                               100                                  100                                     98 75 90    129.        1   PRE 100                   100                      -- 100                            100                               100                                  100                                     100                                        100                                           100        1   POST                80 100                      100                         100                            100                               100                                  95 65 40 80    131.        1   PRE 100                   100                      -- 100                            100                               100                                  100                                     100                                        100                                           95        1   POST                25 100                      100                         100                            65 95 30 100                                        60 0    132.        4   PRE 80 100                      -- 100                            100                               100                                  100                                     85 98 95        4   POST                25 100                      100                         100                            60 85 98 25 0  35    134.        1   PRE 100                   90 -- 100                            100                               100                                  100                                     65 20 60        1   POST                75 50 100                         80 100                               0  25 15 0  0    136.        1   PRE 35 55 -- 100                            100                               100                                  100                                     100                                        30 85        1   POST                35 40 100                         100                            100                               0  100                                     60 0  0    137.        1   PRE 75 100                      -- 100                            100                               100                                  100                                     100                                        0  95        1   POST                55 70 100                         75 100                               0  15 10 40 0    138.        1   PRE 85 100                      -- 100                            100                               100                                  100                                     100                                        0  95        1   POST                70 55 100                         100                            100                               70 98 55 25 0    __________________________________________________________________________     *"--" means not tested

                                      TABLE VII    __________________________________________________________________________    HERBICIDAL ACTIVITY    Com-    pound        Rate    No. (lb./A)            Types                BID                   NS  SMT                          VEL BYG                                 CRB FOX                                        MF    __________________________________________________________________________     33.        1   PRE 50 0   100                          100 100                                 95  100                                        80        1   POST                40 100 100                          100 95 20  75 20     52.        2   PRE 100                   --  100                          100 95 100 100                                        100        1   POST                100                   100 100                          100 40 20  10 0     93.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100     94.        1   PRE 95 40  100                          100 0  100 90 0        1   POST                40 100 70 100 20 40  25 0     95.        1   PRE 100                   100 100                          100 95 100 100                                        100        1   POST                100                   100 100                          100 95 100 100                                        95    121.        1   PRE 100                   --  100                          100 100                                 100 100                                        75        1   POST                100                   100 100                          100 75 75  85 20    123.        1   PRE 100                   100 100                          100 100                                 100 100                                        10        1   POST                75 --  75 100 20 20  90 0    127.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 90 20  100                                        40    130.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 60  100                                        20    133.        1   PRE 100                   100 100                          100 95 100 100                                        100        1   POST                100                   --  100                          100 95 100 100                                        25    135.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   --  100                          100 100                                 100 100                                        95    139.        3   PRE 100                   100 100                          100 100                                 100 100                                        100        3   POST                100                   100 100                          100 100                                 100 100                                        100    140.        1   PRE -- 100 100                          100 98 --  100                                        --        1   POST                -- 100 15 100 100                                 --  70 --    141.        1   PRE -- 100 100                          100 99 --  100                                        --        1   POST                -- 100 100                          100 100                                 --  100                                        --    142.        1   PRE 80 90  100                          100 95 100 100                                        80        1   POST                90 100 100                          100 25 40  50 0    143.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    144.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                95 100 100                          100 100                                 100 100                                        100    145.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   --  100                          100 100                                 100 100                                        100    146.        1   PRE 100                   100 100                          --  100                                 --  100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        95    147.        1   PRE 100                   100 -- 100 95 --  100                                        100        1   POST                100                   100 100                          100 98 85  80 70    148.        1   PRE 90 90  0  100 0  0   0  0        1   POST                0  0   0  0   0  0   0  0    149.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        95    150.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   --  100                          100 100                                 100 100                                        70    151.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   --  100                          100 100                                 100 100                                        90    152.        1   PRE 100                   60  80 100 40 0   0  0        1   POST                80 --  0  100 0  40  20 0    153.        1   PRE 75 50  0  100 25 80  70 0        1   POST                75 80  0  20  10 0   20 0    154.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    155.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    156.        1   PRE 90 100 100                          100 0  100 100                                        90        1   POST                40 100 80 100 10 0   0  30    157.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 90 60    158.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    159.        1   PRE 95 100 100                          100 10 100 100                                        10        1   POST                80 100 100                          100 10 80  20 10    160.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    161.        1   PRE 100                   100 100                          100 0  95  100                                        0        1   POST                35 100 100                          100 40 80  50 0    162.        1   PRE 100                   100 100                          100 50 100 100                                        95        1   POST                95 100 100                          100 100                                 85  90 60    163.        1   PRE 100                   100 100                          100 90 100 100                                        100        1   POST                100                   100 100                          100 100                                 80  90 50    164.        1   PRE 100                   100 100                          100 85 95  100                                        95        1   POST                75 100 100                          100 60 80  60 20    165.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    166.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    167.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 95  100                                        95    168.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    169.        1   PRE 100                   100 100                          100 80 100 100                                        10        1   POST                75 100 100                          100 10 90  25 10    170.        1   PRE 0  0   0  0   0  0   0  0        1   POST                40 60  0  0   0  0   0  0    171.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                75 --  100                          100 100                                 100 100                                        60    172.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    173.        1   PRE 95 100 100                          100 80 100 100                                        50        1   POST                100                   100 100                          100 100                                 100 100                                        50    174.        1   PRE 85 100 100                          100 90 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    175.        1   PRE 25 100 100                          100 0  100 100                                        100        1   POST                30 --  100                          100 60 90  80 75    176.        1   PRE 95 100 100                          100 95 100 100                                        95        1   POST                95 --  100                          100 95 100 95 75    177.        1   PRE 90 100 100                          100 95 100 100                                        40        1   POST                100                   --  100                          100 95 100 100                                        50    178.        1   PRE 40 0   100                          90  0  100 100                                        25        1   POST                100                   100 100                          100 75 60  90 50    179.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 95 100    180.        1   PRE 10 100 0  95  0  95  95 0        1   POST                75 80  0  40  0  90  40 0    181.        1   PRE 100                   100 100                          100 75 100 100                                        95        1   POST                100                   100 100                          100 100                                 100 100                                        75    182.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    183.        1   PRE 0  0   0  0   0  0   0  0        1   POST                10 20  20 0   0  0   0  0    184.        1   PRE 100                   0   100                          100 95 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        70    185.        1   PRE 0  0   0  50  0  0   0  0        1   POST                50 75  0  35  0  20  0  0    186.        1   PRE 95 100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        60    187.        1   PRE 90 100 100                          100 95 100 100                                        95        1   POST                95 100 100                          100 100                                 100 100                                        50    188.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    189.        1   PRE 100                   100 100                          100 95 100 100                                        100        1   POST                95 100 100                          100 95 95  100                                        80    190.        1   PRE 100                   100 100                          100 90 100 100                                        95        1   POST                100                   100 95 100 95 100 100                                        95    191.        1   PRE 100                   50  0  100 0  100 95 25        1   POST                80 95  20 95  20 50  40 0    192.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    193.        1   PRE 100                   100 95 100 95 100 100                                        95        1   POST                100                   100 100                          100 95 90  95 75    194.        1   PRE 95 100 100                          100 100                                 100 100                                        95        1   POST                100                   100 100                          100 100                                 100 100                                        95    195.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    196.        1   PRE 100                   100 -- 100 95 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    197.        1   PRE 100                   80  100                          100 100                                 100 100                                        95        1   POST                100                   100 100                          100 100                                 95  100                                        95    198.        1   PRE 75 90  0  100 0  60  0  0        1   POST                0  0   0  0   0  0   0  0    199.        1   PRE 100                   0   100                          100 95 100 100                                        75        1   POST                100                   100 100                          100 100                                 95  100                                        95    200.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                90 100 100                          100 80 50  90 10    201.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 95  100                                        100    202.        1   PRE 50 85  100                          100 10 95  100                                        90        1   POST                20 20  60 20  0  0   0  0    203.        1   PRE 100                   100 100                          100 80 100 100                                        90        1   POST                100                   100 100                          100 95 95  100                                        95    204.        1   PRE 95 100 100                          100 95 100 100                                        100        1   POST                95 100 100                          100 80 0   60 50    205.        1   PRE 90 90  90 100 20 80  95 40        1   POST                10 100 90 50  0  0   0  0    206.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    207.        1   PRE 95 100 100                          100 95 95  100                                        100        1   POST                100                   100 100                          100 100                                 85  100                                        95    208.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 95 75  100                                        100    209.        1   PRE 40 20  100                          100 0  95  100                                        80        1   POST                85 100 95 100 60 60  85 40    210.        1   PRE 100                   100 100                          100 95 100 100                                        100        1   POST                95 100 100                          100 95 80  95 90    211.        1   PRE 100                   40  100                          100 40 100 100                                        90        1   POST                90 60  100                          95  60 10  40 10    212.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    213.        1   PRE 0  0   0  100 0  0   0  0        1   POST                100                   100 100                          100 100                                 95  100                                        75    214.        1   PRE 0  0   100                          0   0  0   0  0        1   POST                0  0   0  0   0  0   0  0    215.        1   PRE 95 90  100                          100 35 90  100                                        90        1   POST                100                   100 100                          100 95 100 100                                        90    216.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    217.        1   PRE 100                   95  100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 75  100                                        80    218.        1   PRE 100                   90  100                          100 100                                 100 100                                        95        1   POST                100                   100 100                          100 100                                 100 100                                        95    219.        1   PRE 80 70  100                          100 95 100 100                                        50        1   POST                100                   100 100                          100 95 100 100                                        70    220.        1   PRE 80 0   95 100 80 100 100                                        40        1   POST                100                   95  100                          100 60 30  100                                        20    221.        1   PRE 0  10  100                          100 25 80  95 0        1   POST                100                   100 100                          100 70 95  100                                        25    222.        1   PRE 0  0   0  0   0  0   0  0        1   POST                25 80  0  95  0  0   0  0    223.        1   PRE 70 10  100                          100 100                                 100 100                                        80        1   POST                100                   100 100                          100 100                                 100 100                                        50    224.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    225.        1   PRE 0  0   0  75  0  0   0  0        1   POST                90 100 80 100 0  0   20 0    226.        1   PRE 70 10  20 75  40 80  100                                        25        1   POST                90 100 100                          90  25 0   60 10    227.        1   PRE 95 90  80 100 70 100 100                                        80        1   POST                100                   100 100                          100 100                                 80  100                                        90    228.        1   PRE 90 95  100                          100 95 100 100                                        100        1   POST                75 100 100                          100 95 90  70 70    229.        1   PRE 95 100 0  95  0  70  90 0        1   POST                80 100 10 100 10 20  25 0    230.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    231.        1   PRE 70 80  90 100 90 100 100                                        95        1   POST                0  0   0  0   0  0   0  0    232.        1   PRE 85 100 100                          100 100                                 100 100                                        100        1   POST                95 100 100                          100 100                                 75  100                                        80    233.        1   PRE 85 100 100                          100 100                                 100 100                                        100        1   POST                40 100 100                          95  100                                 25  90 40    234.        1   PRE 95 100 100                          100 10 90  100                                        90        1   POST                40 100 100                          100 0  0   50 0    235.        1   PRE 100                   --  -- 100 95 100 100                                        100        1   POST                95 100 100                          100 100                                 70  95 80    236.        1   PRE 100                   100 100                          100 95 100 100                                        100        1   POST                100                   100 100                          100 85 75  80 20    237.        1   PRE 100                   100 100                          100 95 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    238.        1   PRE 100                   100 100                          100 100                                 100 100                                        100        1   POST                100                   100 100                          100 100                                 100 100                                        100    239.        1   PRE 95 100 100                          100 25 100 100                                        10        1   POST                100                   100 100                          100 60 75  85 0    240.        1   POST                100                   100 100                          100 100                                 100 100                                        100    241.        1   POST                95 100 100                          100 95 95  60 95    242.        1   POST                100                   100 100                          100 100                                 100 100                                        95    243.        1   PRE 100                   100 100                          100 80 100 90 100        1   POST                100                   100 100                          100 100                                 95  50 80    244.        1   PRE 60 95  0  95  40 100 80 85        1   POST                70 100 100                          100 10 10  35 20    245.        1   PRE 0  80  0  90  0  95  80 0        1   POST                90 100 85 100 10 25  30 0    246.        1   PRE 60 90  40 100 0  80  20 10        1   POST                75 95  95 50  0  0   10 0    __________________________________________________________________________     *"--" means not tested

The glutarimide compounds of the instant invention are also useful asalgicides. The compounds may be advantageously used to either prevent orcontrol the growth of algae. The exact amount of glutarimide requiredwill, of course, vary with the medium being protected, the algae beingcontrolled, the particular glutarimide being employed and other factorsknown to one skilled in the art.

The glutarimides of the present invention, when used for the control ofalgae, can be used in any of the types of formulations disclosed abovefor the control of undesired plants. These formulations include liquidsolutions, such as emulsifiable concentrates and dilute sprays, and drypowders such as wettable powders and dusts.

The algicidal and algistatic activities of the compounds of the instantinvention were determined by the following procedure.

In separate wells of a microtiter plate (Plate A) were placed 100 μlserial dilutions of the compound to be tested in modified Allen'smedium, described below. In addition, one well contained only modifiedAllen's medium (no compound) as a control. Each well of the plate wasthen inoculated with a mixed algae culture. After 4 hours, a 5 μlaliquot of each well was removed and placed in a different microtiterplate well (Plate B) containing 100 μl of Allen's modified medium. Theplates were covered with dear plastic lids and placed in a dear plasticbag along with several moistened paper towels to create high humidityand prevent evaporation from the plates.

The plastic bags containing the plates were placed in high lightconditions (200-700 foot candles) at room temperature. After 5 or 14days the minimal inhibitory concentration (MIC) needed to inhibit growthwas determined from Plate A. The effect of inhibiting growth is definedas the static effect. After 8-10 days, the 4-hour tidal effect (killingof the organism) of the compound was determined from Plate B. To readthe microtiter plates for static or cidal activity, a stereoscope wasused at low magnification to observe growth or no growth in each well.Plate readers were also used to read growth or no growth.

The following procedure was used to prepare modified Allen's medium.

Seven stock solutions were prepared as follows:

    ______________________________________    NaNO.sub.3  10.0 g in 400 ml deionized water    CaCl.sub.2  1.0 g in 400 ml deionized water    MgSO.sub.4.7H.sub.2 O                3.0 g in 400 ml deionized water    K.sub.2 HPO.sub.4                3.0 g in 400 ml deionized water    KH.sub.2 PO.sub.4                7.0 g in 400 ml deionized water    NaCl        1.0 g in 400 ml deionized water    FeCl.sub.3  1.0 g in 100 ml deionized water    ______________________________________

Each of the above stock solutions was filter sterilized.

To 940 ml of sterile deionized water, was added 1 drop of the FeCl₃solution and 10.0 ml of all the other stock solutions. The ambient pH ofthis medium was about 6.1 and the water hardness was about 65 ppm,expressed as calcium carbonate. The pH and hardness was adjusted to thepH value of Table VIII with sterile 1 normal (N) KOH or HCl for pH andthe water hardness of Table VIII with a sterile NaHCO₃ solution (56.03 gNaHCO₃ in 1.0 liter of boiled and distilled water, then filtered andsterilized.

The mixed algae culture was obtained from an industrial cooling tower inSpring House, PA and maintained in the laboratory by means commonlyknown. The mixed culture contained green algae and blue-green bacteria.

The algicidal activity (in ppm) of compounds of the present invention inmodified Allen's medium under 750 foot candles of light is shown inTable VIII.

                  TABLE VIII    ______________________________________    Algicidal Activity                           pH 6.1         pH 8    Compound     No. of    393 ppm*       200 ppm    No.          Days      static  cidal  static    ______________________________________    Test 1 10         5        <0.015                                     <2      --**    Test 2 10         5        0.25  --     --           85         5        0.125 --     --           51         5        0.25  --     --    Test 3  2        14                      32           12        14                      32           19        14                     125           27        14                     125           34        14                     125           38        14                      63           41        14                      63           45        14                     <2           46        14                      4           49        14                      32           56        14                     250           57        14                      32           62        14                      63           64        14                     125           76        14                     125           78        14                     250           80        14                      63           81        14                      63           87        14                     125           91        14                      63           92        14                     125           99        14                     250           110       14                      63           114       14                     <2           148       14                     125    ______________________________________     *ppm water hardness, expressed as calcium carbonate     **not tested

It is to be understood that changes and variations may be made withoutdeparting from the spirit and scope of the invention as defined by theappended claims.

What is claimed is:
 1. A herbicidal compound of the formula ##STR60##wherein A is carbonyl, thiocarbonyl or methylene;A¹ is carbonyl ormethylene; Q is (CH₂)_(n), where n is 0 or 1, or oxygen; R is (C₁-C₄)alkyl, (C₁ -C₄)haloalkyl containing from one to nine halo atoms, orphenyl; R¹ is hydrogen or (C₁ -C₂)alkyl; R² is hydrogen; or R, R¹ and R²taken together form a fused phenyl ring; X is hydrogen, cyano orhalogen; T is hydrogen or fluorine; and Z and Y together form a6-membered heterocyclic ring fused to the phenyl ring structure to forma bicyclic moiety having the structure ##STR61## wherein L is oxygen R³is hydrogen or alkyl; R⁴ is hydrogen; alkyl; alkenyl; alkynyl;alkoxyalkyl; alkenyloxyalkyl; alkynyloxyalkyl; alkoxycarbonylalkyl;cycloalkyl; cycloalkylalkyl; alkylaminoalkyl; alkylaminocarbonylalkyl;heterocyclyl or heterocyclyl(C₁ -C₆)alkyl wherein the heterocyclyl groupis a three to six membered heterocyclic ring containing one, two orthree hetero atoms selected from the group consisting of oxygen,nitrogen and sulfur: alkoxycarbonylalkyl, phenylalkyl; alkylthioalkyl;alkenylthioalkyl; alkynylthioalkyl; alkoxycarbonyl; or alkanoyl;and theagronomically acceptable salts thereof.
 2. The compound of claim 1whereinA is C═O, C═S or CH₂ ; A¹ is C═O or CH₂ ; Q is (CH₂)_(n), where nis 0 or 1, or oxygen; R is (C₁ -C₄)alkyl, (C₁ -C₄)haloalkyl or phenyl;R¹ is H or (C₁ -C₂)alkyl; R² is H or, together with R and R¹, fusedphenyl; X is H, Cl, Br, CN or F; T is H or F; Z and Y together form a6-membered heterocyclic ring fused to the phenyl ring structure to forma bicyclic moiety having the structure ##STR62## wherein R³ is hydrogenor (C₁ -C₃)alkyl; and R⁴ is hydrogen; (C₁ -C₈)alkyl; (C₃ -C₆)alkenyl;(C₃ -C₆)alkynyl; (C₁ -C₆)alkoxy(C₁ -C₆)alkyl; (C₁ -C₆)alkylthio(C₁-C₆)alkyl; (C₃ -C₆)cycloalkyl, (C₃ -C₆)cycloalkyl(C₁ -C₆)alkyl;heterocyclyl or heterocyclyl(C₁ -C₆)alkyl wherein the heterocyclyl groupis a three to six membered heterocyclic ring containing one, two orthree hetero atoms selected from the group consisting of oxygen,nitrogen and sulfur: di(C₁ -C₆)alkylamino(C₁ -C₆)alkyl; di(C₁-C₆)alkylaminocarbonyl(C₁ -C₆)alkyl; phenyl(C₁ -C₆)alkyl; cyano(C₁-C₆)alkyl; (C₁ -C₆)alkoxycarbonyl(C₁ -C₆)alkyl; (C₁ -C₆)alkoxycarbonyl;or (C₁ -C₆)alkanoyl; andthe agronomically acceptable salts thereof. 3.The compound of claim 2 wherein Z and Y together form a 6-memberedheterocyclic ring fused to the phenyl ring structure to form a bicyclicmoiety having the structure ##STR63## wherein A and A¹ are C═O;Q is(CH₂)_(n), where n is 0; L is O; X is H or F: R is (C₁ -C₄)alkyl, (C₁-C₄)haloalkyl or phenyl; R¹ is H or (C₁ -C₂)alkyl; R² is H or, togetherwith R and R¹, fused phenyl; R³ is H or (C₁ -C₃)alkyl; and R⁴ ishydrogen, (C₁ -C₈)alkyl, (C₃ -C₆)alkenyl, (C₃ -C₆)alkynyl, (C₁-C₆)alkoxy(C₁ -C₆)alkyl, (C₁ -C₆)alkylthio(C₁ -C₆)alkyl, phenyl(C₁-C₆)alkyl, cyano(C₁ -C₆)alkyl, (C₁ -C₆)alkoxycarbonyl(C₁ -C₆)alkyl;alkylaminocarbonylalkyl; heterocyclyl or heterocyclyl(C₁ -C₆)alkylwherein the heterocyclyl group is a three to six membered heterocyclicring containing one, two or three hetero atoms selected from the groupconsisting of oxygen, nitrogen and sulfur; alkoxycarbonylalkyl;alkylaminoalkyl; (C₁ -C₆)alkoxycarbonyl or (C₁ -C₆)alkanoyl; and theagronomically acceptable salts thereof.
 4. The compound of claim 3 ofthe formula ##STR64## wherein L is 0;X is H or F; R is CH₃, CHF₂, CFH₂or CF₃ ; R³ is H or (C₁ -C₃)alkyl; and R⁴ is hydrogen, (C₁ -C₈)alkyl,(C₃ -C₆)alkenyl, (C₃ -C₆)alkynyl, (C₁ -C₆)alkoxymethyl, (C₁-C₆)alkylthiomethyl, halo(C₃ -C₆)alkenyl, (C₃ -C₆)cycloalkyl(C₁-C₆)alkyl, heterocyclyl or heterocyclyl(C₁ -C₆)alkyl wherein theheterocyclyl group is a three to six membered heterocyclic ringcontaining one, two or three hetero atoms selected from the groupconsisting of oxygen, nitrogen and sulfur; di(C₁ -C₆)alkylamino(C₁-C₆)alkyl, di(C₁ -C₆)alkylaminocarbonyl(C₁ -C₆)alkyl or cyano(C₁-C₆)alkyl.
 5. The compound of claim 4 wherein X is H or F, R is CH₃,CHF₂ or CF₃, R³ is H, CH₃ or CH₂ CH₃, and R⁴ is propargyl, allyl,ethoxymethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl,1-ethylpropyl, 2-methoxyethyl, methoxymethyl, methylthiomethyl,1-cyanoethyl, 1-methylpropargyl, 2-methylallyl, cyanomethyl,cyclopropylmethyl, cyclopentyl, dimethylaminocarbonylmethyl,2-tetrahydrofuranylmethyl, 3-tetrahydrofuranyl, 2-chloroallyl, or3,3-dichloroallyl.
 6. The compound of claim 5 wherein L is oxygen, R isCH₃, R³ is H, R⁴ is propargyl and X is F.
 7. The compound of claim 5wherein R is CF₃, R³ is CH₃, R⁴ is propargyl, L is oxygen and X is H orF.
 8. The compound of claim 5 wherein R is CF₃, R³ and X are H, L isoxygen and R⁴ is propargyl, n-propyl, 1-methylpropargyl, allyl, s-butyl,methoxymethyl or 2-methoxyethyl.
 9. The compound of claim 5 wherein R isCF₃, R³ is H, X is F, L is oxygen and R⁴ is propargyl, cyanomethyl,allyl, methoxymethyl, ethoxymethyl, n-propyl, isopropyl, n-butyl,isobutyl, s-butyl, 1-cyanoethyl, 2-methylallyl, methylthiomethyl,2-ethylpropyl, cyclopropylmethyl, cydopentyl,dimethylaminocarbonylmethyl, 2-tetrahydrofuranylmethyl,3-tetrahydrofuranyl, 2-chloroallyl, 3,3-dichloroallyl or ethyl.
 10. Thecompound of claim 5 wherein R is CHF₂, R³ is H, L is oxygen, X is F andR⁴ is allyl.
 11. The compound of claim 5 wherein R is CF₃, R³ is CH₂CH₃, L is oxygen, X is F, and R⁴ is propargyl.
 12. The compound of claim5 wherein R is CF₃, R³ is H, L is sulfur, X is F and R⁴ is propargyl.13. The compound of claim 1 which is7-fluoro-4-methoxymethyl-6-(N-(3-(trifluoromethyl)-glutarimido))-2H-1,4-benzoazin-3-(4H)one.
 14. A herbicidal composition comprising anagronomically acceptable carrier and a herbicidally effective amount ofthe compound of claim
 1. 15. A herbiddal composition comprising anagronomically acceptable carrier and a herbicidally effective amount ofthe compound of claim
 2. 16. A method for controlling unwanted plantswhich comprises applying to the plant or growth medium therefore thecompound of claim
 1. 17. A method for controlling unwanted plants whichcomprises applying to the plant or growth medium therefore the compoundof claim
 2. 18. The method of claim 16 wherein the compound is appliedpreemergence.
 19. The method of claim 16 wherein the compound is appliedpostemergence.
 20. A method for controlling unwanted plants whichcomprises applying to the the plant or growth medium the compound ofclaim 13.